Analgesic efficacy of bromfenac, ibuprofen, and aspirin in postoperative oral surgery pain. Evaluation of different doses of soluble ibuprofen and ibuprofen tablets in postoperative dental pain. Analgesic dose-response relationship of ibuprofen 50, 100, 200, and 400 mg after surgical removal of third molars: a single-dose, randomized, placebo-controlled, and double-blind study of 304 patients. A double-blind, randomized study of naproxen sodium, ibuprofen, and placebo in postoperative dental pain. Comparative study of ibuprofen lysine and acetaminophen in patients with postoperative dental pain. Premedication with pregabalin 75 or 150 mg with ibuprofen to control pain after day-case gynaecological laparoscopic surgery. The comparative efficacy of aceclofenac and ibuprofen in postoperative pain after third molar surgery. Single dose and multidose analgesic study of ibuprofen and meclofenamate sodium after third molar surgery. Analgesic efficacy of celecoxib in postoperative oral surgery pain: a single-dose, two-center, randomized, double-blind, active- and placebo-controlled study. Ibuprofen and acetaminophen in the relief of postpartum episiotomy pain. Analgesic effect of fendosal, ibuprofen and aspirin in postoperative oral surgery pain. Multicenter clinical trial of ibuprofen and acetaminophen in the treatment of postoperative dental pain. The efficacy of a novel adenosine agonist (WAG 994) in postoperative dental pain. Comparison of single-dose ibuprofen lysine, acetylsalicylic acid, and placebo for moderate-to-severe postoperative dental pain. An evaluation of different ibuprofen preparations in the control of postoperative pain after third molar surgery. Evaluation of bromfenac, aspirin, and ibuprofen in postoperative oral surgery pain. Analgesic efficacy of two ibuprofen-codeine combinations for the treatment of postepisiotomy and postoperative pain. MK-0703 (a cyclooxygenase-2 inhibitor) in acute pain associated with dental surgery: a randomized, double-blind, placebo- and active comparator-controlled dose-ranging study. Dose-response of flurbiprofen on postoperative pain and emesis after paediatric strabismus surgery. Comparison of the analgesic efficacy of concurrent ibuprofen and paracetamol with ibuprofen or paracetamol alone in the management of moderate to severe acute postoperative dental pain in adolescents and adults: a randomized, double-blind, placebo-controlled, parallel-group, single-dose, two-center, modified factorial study. Multimodal analgesia before thoracic surgery does not reduce postoperative pain. Ibuprofen arginate provides effective relief from postoperative dental pain with a more rapid onset of action than ibuprofen. Evaluation of ketorolac, ibuprofen, acetaminophen, and an acetaminophen-codeine combination in postoperative oral surgery pain. Analgesic efficacy of a hydrocodone with ibuprofen combination compared with ibuprofen alone for the treatment of acute postoperative pain. Ibuprofen plus codeine, ibuprofen, and placebo in a single- and multidose cross-over comparison for coxarthrosis pain. Ibuprofen and acetaminophen in the relief of acute pain: a randomized, double-blind, placebo-controlled study. Analgesic efficacy of single oral doses of lumiracoxib and ibuprofen in patients with postoperative dental pain. A placebo-controlled comparative evaluation of diclofenac dispersible versus ibuprofen in postoperative pain after third molar surgery. A single-tablet fixed-dose combination of racemic ibuprofen/paracetamol in the management of moderate to severe postoperative dental pain in adult and adolescent patients: a multicenter, two-stage, randomized, double-blind, parallel-group, placebo-controlled, factorial study. Analgesic efficacy of the cyclooxygenase-2-specific inhibitor rofecoxib in post-dental surgery pain: a randomized, controlled trial. A randomised, five-parallel-group, placebo-controlled trial comparing the efficacy and tolerability of analgesic combinations including a novel single-tablet combination of ibuprofen/paracetamol for postoperative dental pain. A randomized, double-blind, placebo-controlled comparison of the analgesic efficacy, onset of action, and tolerability of ibuprofen arginate and ibuprofen in postoperative dental pain. Analgesic efficacy of low-dose ibuprofen in dental extraction pain. [Analgesic effect of ibuprofen in pain after episiotomy]. A double-blind comparison of parenteral morphine, placebo, and oral fenoprofen in management of postoperative pain. Effect of caffeine on ibuprofen analgesia in postoperative oral surgery pain. Evaluation of the dose range of etoricoxib in an acute pain setting using the postoperative dental pain model. Ibuprofen liquigel for oral surgery pain. Onset and duration of analgesia for low-dose ketoprofen in the treatment of postoperative dental pain. The analgesic efficacy of diclofenac dispersible and ibuprofen in postoperative pain after dental extraction. Codeine 20 mg increases pain relief from ibuprofen 400 mg after third molar surgery. A repeat-dosing comparison of ibuprofen and an ibuprofen-codeine combination. Analgesic efficacy of a combination of hydrocodone with ibuprofen in postoperative pain. Comparison of an antiinflammatory dose of ibuprofen, an analgesic dose of ibuprofen, and acetaminophen in the treatment of patients with osteoarthritis of the knee. Efficacy and quality of ibuprofen and acetaminophen plus codeine analgesia. Comparison of postoperative analgesic effects of preemptively used epidural ketamine and neostigmine. Enhanced analgesia and suppression of plasma beta-endorphin by the S(+)-isomer of ibuprofen. A multiple dose comparison of ibuprofen and dihydrocodeine after third molar surgery. Non-steroidal anti-inflammatory drugs in treatment of postoperative pain after cardiac surgery. Analgesic effect of graded doses of flurbiprofen in post-episiotomy pain. An evaluation of flurbiprofen, aspirin, and placebo in postoperative oral surgery pain. Ibuprofen compared with ibuprofen plus caffeine after third molar surgery. Ibuprofen does not impair renal function in patients undergoing infrarenal aortic surgery with epidural anaesthesia. [Does the preoperative administration of ketorolac improve postoperative analgesia]. The IPSO study: ibuprofen, paracetamol study in osteoarthritis. A randomised comparative clinical study comparing the efficacy and safety of ibuprofen and paracetamol analgesic treatment of osteoarthritis of the knee or hip. Narcotic receptor blockade and its effect on the analgesic response to placebo and ibuprofen after oral surgery.
We recently demonstrated that 25 mg of bromfenac, a new nonsteroidal anti-inflammatory analgesic, is at least as effective as 400 mg of ibuprofen in relieving postoperative oral surgery pain. Our objective in this study was to determine whether higher doses were significantly more effective. Two hundred eighty (280) outpatients with postoperative pain after the surgical removal of impacted third molars were randomly assigned, on a double-blind basis, a single oral dose of 10, 25, 50, or 100 mg bromfenac; 650 mg aspirin; 400 mg ibuprofen; or placebo. Subjects rated their pain and its relief for 8 hours. All active treatments were significantly superior to placebo, and bromfenac and ibuprofen were significantly superior to aspirin. The slope of the dose-response curve of bromfenac was significant. The 100 mg bromfenac dose was significantly more effective than the 400 mg ibuprofen dose and had a significantly longer duration of analgesic action. The object of the study was to assess the comparative efficacy of three single doses (200, 400, 600 mg) of soluble ibuprofen and ibuprofen tablets after third molar surgery in 148 patients and aged 18-40 years. Outcome was measured by overall assessment of pain (AUC360) assessed from serial visual analogue scales, the number of patients taking additional analgesic and by overall assessment of medication evaluated on a five-point categorical scale. Over the 6-hour investigation period all the ibuprofen treatments with the exception of ibuprofen tablets 200 mg resulted in significantly less pain (p < 0.05) than placebo treatment. A large number of patients required additional analgesia during the investigation period, but the time to taking it was significantly earlier in the placebo group. No significant dose response (p > 0.05) was observed for either ibuprofen preparations assessed by the outcome variable of overall pain experience (AUC360) or time to additional analgesia. There was no significant difference in pain scores or time to taking additional analgesics between the respective doses of soluble and tablet formulations of ibuprofen. Both soluble and tablet formulations of ibuprofen provide effective pain control in the early postoperative period after removal of impacted third molars. There is little analgesic advantage in increasing the dose to 600 mg and only minimal benefit from using a soluble formulation of the drug. The purpose of this single-dose, randomized, placebo-controlled, and double-blind study was to evaluate the analgesic dose-response relationship of 50-mg, 100-mg, 200-mg, and 400-mg doses of ibuprofen after third molar surgery. Patients were instructed to take a single dose of either placebo or 50 mg, 100 mg, 200 mg, or 400 mg of ibuprofen when the postoperative pain was moderate to severe. Acetaminophen 500 mg was used as a rescue medication. Pain intensity, pain relief, and any possible adverse events were recorded on self-administered questionnaires hourly for 6 hours after intake of study medication. If rescue medication was taken, the time of intake was registered. A total of 304 patients entered the study, and 258 complied with the protocol. A positive analgesic dose-response relationship of 50-mg, 100-mg, 200-mg, and 400-mg doses of ibuprofen was observed when evaluated by pain intensity difference, sum of pain intensity difference, pain relief, total pain relief, and survival distribution of patients not taking rescue medication. Although significant pain relief was seen after a dose of 50 mg ibuprofen, ibuprofen 400 mg provided maximum pain relief and the longest duration of analgesic effect. Mild transient adverse events were reported by 6.8% of the patients. However, there was no significant difference in frequency between the placebo and 50 mg, 100 mg, 200 mg, and 400 mg ibuprofen dose groups. In a double-blind, parallel, placebo-controlled study, 203 patients with post-operative dental pain following the extraction of one or two bony impacted third molars were randomized to receive a single dose of naproxen sodium 220 mg, ibuprofen 200 mg or placebo. Pain intensity and pain relief were assessed at intervals for 12 hours postdose. Both active drugs demonstrated superior analgesic efficacy over placebo. Naproxen sodium and ibuprofen were comparable both in onset of analgesic action and in pain relief. From 1 to 12 hours postdose, naproxen sodium showed a trend for superior analgesic efficacy compared with ibuprofen; this trend reached statistical significance at the 12-hour time point. Both drugs were well-tolerated and effective analgesics for postoperative dental pain. This single-dose, double-blind, parallel-group, single-site study compared ibuprofen lysine 400 mg with acetaminophen 1000 mg and placebo in 240 patients with moderate-to-severe postoperative dental pain. The relative onset of analgesic response, overall analgesic efficacy, duration of effect, and safety were assessed over a 6-hour postdose period. Analgesic efficacy was assessed by patient self-rating of pain intensity, pain relief, time to meaningful pain relief, need for additional analgesic medication, and patient global evaluation. Both ibuprofen lysine 400 mg and acetaminophen 1000 mg were significantly (P < or = 0.05) more effective than placebo. Ibuprofen lysine had a significantly (P < or = 0.05) faster onset of action with greater peak and overall analgesic effect than did effect than did acetaminophen. All treatments were generally well tolerated. Multimodal pain management has been suggested to improve postoperative analgesia. In this study, we evaluated the quality of analgesia in women undergoing day-case gynaecological laparoscopic surgery, after premedication with pregabalin 75 mg (P75) or 150 mg (P150), compared with diazepam 5 mg (D5). All patients were given ibuprofen 800 mg orally.
                Altogether 90 consenting women were anaesthetized in a standardized fashion. Postoperative analgesia was provided by ibuprofen 800 mg twice a day with fentanyl i.v. on request in the recovery room (RR), and combination tablets with acetaminophen and codeine after the RR. The visual analogue scale (VAS) scores for pain and side-effects and the amounts of postoperative analgesics were recorded for 24 h after surgery. The areas under the curves (AUC) were calculated for the VAS scores for pain at rest, pain in motion, and pain at cough 1-8 and 1-24 h after surgery.
                The median AUC values for VAS scores for pain at rest (P=0.048) and in motion (P=0.046) 1-8 h after surgery were lower in the P150 group than that in the D5 group. The amounts of rescue analgesics or the degree of drowsiness did not differ in the three study groups.
                Analgesia was better after premedication with pregabalin 150 mg than after diazepam 5 mg, both with ibuprofen 800 mg, during the early recovery after day-case gynaecological laparoscopic surgery. Pregabalin 150 mg did not reduce the amount of postoperative analgesics required. The aim of the present placebo-controlled, double-blind study was to evaluate the comparative efficacy of single doses of aceclofenac 150 mg and ibuprofen 400 mg in 217 patients with postoperative pain after third molar surgery. Outcome of primary efficacy was judged by overall assessment of the area under the curve (AUC) of graphs for pain intensity (AUC pain) pain relief (AUC relief), both measured from serial visual analogue scales over a 6 h investigation period. Other measures of efficacy included the rate of pain reduction in the first hour, the number of patients who took 'escape' analgesics and the time before they did, and an overall assessment of pain relief score on a five-point categorical scale. Ibuprofen 400 mg was significantly superior to placebo for pain relief (P < 0.01), degree of pain reduction in the first hour (P = 0.005), and the number of patients who required escape analgesia (P < 0.001), and the time before they did (P < 0.001). The outcome for patients treated with aceclofenac 150 mg was not significantly different from that of patients treated with placebo (P > 0.05). A single dose of ibuprofen 400 mg provided significant pain relief in the early postoperative period after third molar surgery, whereas a single dose of aceclofenac 150 mg was not effective in the management of postoperative pain after this operation. The purpose of this study was to compare the analgesic efficacy and safety of meclofenamate sodium with ibuprofen after dental impaction surgery. This study was double-blind and used a unique methodology. Patients (N = 254) were first randomized into the single dose phase of the study that included placebo, meclofenamate 50 mg, meclofenamate 100 mg, ibuprofen 200 mg, and ibuprofen 400 mg, followed by a 7-day multidose phase in which patients in the placebo group were rerandomized into one of the active treatment cells. In the single dose phase, all active treatments were significantly more efficacious than placebo for every summary analgesic measure. A positive dose-response was seen for both active drugs with meclofenamate 100 mg and ibuprofen 400 mg exhibiting the greatest efficacy for pain relief, pain reduction, time to remedication, and overall evaluation. Side effects were reported by 26 patients. They were evenly distributed among treatment groups with headache and drowsiness being the most common. During the multidose phase, there were only small differences in efficacy measures among active treatment groups. However, meclofenamate produced a higher incidence of stomach cramps and diarrhea than did ibuprofen (8.8% and 7.2% versus 0.8% and 0.8%). This study indicates that higher doses of nonsteroidal anti-inflammatory drugs are most effective immediately after surgery and that lower doses of these drugs can be used after the first postoperative day. The side effect profile of nonsteroidal anti-inflammatory analgesics is best observed with the use of a multidose study design. Celecoxib 200 mg has been reported to reduce pain following dental extraction but to offer poorer pain relief than active comparators.
                The aim of this study was to compare the efficacy and tolerability of celecoxib 400 mg, the recommended loading dose for treatment of acute pain, with that of ibuprofen 400 mg and placebo following oral surgery.
                This was a single-dose, 2-center, randomized, double-blind, active- and placebo-controlled study in which patients with moderate to severe pain following third molar extraction were randomized to receive a single dose of celecoxib 400 mg, ibuprofen 400 mg, or placebo. Pain assessments were completed using a 4-point pain intensity scale where 0=no pain and 3=severe pain and a 5-point pain relief scale where 0=no pain relief and 4= complete pain relief at baseline and 18 time points over 24 hours. Primary efficacy outcome measures were time to onset of analgesia (the median time to perceptible pain relief in those patients who achieved meaningful pain relief), time-specific pain intensity difference (PID), time-specific pain relief (PR), time-specific sum of PID and PR, and time to use of rescue medication. Times to perceptible and meaningful pain relief (secondary efficacy outcome measures) were recorded using 2 stopwatches. Tolerability was assessed through recording of adverse events, clinical laboratory tests, and physical examinations (including collection of vital signs).
                One hundred seventy-one patients were randomized to celecoxib 400 mg (30 women and 27 men; mean [SD] age, 21.4 [4.2] years); ibuprofen 400 mg (30 women and 27 men; mean [SD] age, 22.0 [4.7] years); or placebo (34 women and 23 men; mean [SD] age, 21.6 [5.0] years). Mean times to onset of analgesia with celecoxib 400 mg and ibuprofen 400 mg were rapid and comparable (median 28 minutes and 26 minutes, respectively) and were significantly shorter than with placebo (>24 hours) (both, P<0.05 vs placebo). Compared with placebo, mean time-specific PID scores were significantly greater with celecoxib from 0.5 to 24 hours and with ibuprofen from 0.5 to 16 hours (all, P<0.05 vs placebo). Time-specific PR scores with celecoxib and ibuprofen were significantly greater from 0.75 and 0.5 hour, respectively, compared with placebo (all, P<0.05 vs placebo). PID was significantly greater with celecoxib compared with ibuprofen beginning at 11 hours (all, P<0.05). PR scores were significantly higher with celecoxib versus ibuprofen beginning at 9 hours (all, P<0.05). Median (95% CI) time to use of rescue medication with celecoxib (>24 hours) was significantly longer than with ibuprofen (10 hours, 58 minutes [8 hours, 30 minutes- 14 hours, 34 minutes]) or placebo (1 hour, 51 minutes [1 hour, 40 minutes-2 hours, 22 minutes]) (both, P<0.05). The 3 most common adverse events experienced in the celecoxib group were headache (9 [15.8%] patients), nausea (9 [15.8%] patients), and dizziness (6 [10.5%] patients).
                In this postsurgical dental pain study, the onset and magnitude of pain relief with celecoxib 400 mg and ibuprofen 400 mg were found to be comparable. In addition, patients who received celecoxib 400 mg as a single dose had a significantly longer time to use of rescue medication and had higher pain relief scores later in the study than those who received ibuprofen 400 mg. Celecoxib was well tolerated compared with placebo. A single-dose, double-blind, randomized clinical trial was conducted to examine the relative analgesic efficacy of ibuprofen 400 mg (n = 36), acetaminophen 1000 mg (n = 37), and placebo (n = 38) in postpartum patients who had moderate to severe pain after episiotomy. At regular intervals over 4 hours, patients evaluated pain severity and relief on categorical scales and completed a categorical overall evaluation at the end of the trial. Both active agents were effective compared with placebo (P less than .05). Ibuprofen 400 mg was more effective than acetaminophen 1000 mg for the sum of pain intensity difference, total pain relief, and reduction of pain by more than 50% (P less than .05), suggesting a more rapid onset of action and a more prolonged effect by ibuprofen 400 mg. No adverse effects were reported. Based on the results of this conventional postpartum episiotomy pain model, both agents are considered efficacious and ibuprofen 400 mg is a more effective analgesic for the relief of acute pain than acetaminophen 1000 mg. The analgesic efficacy of a single 200-mg dose of fendosal, a nonnarcotic, nonsteroidal antiinflammatory analgesic, was compared, in a double-blind study, with aspirin 650 mg, ibuprofen 400 mg and placebo in outpatients who had moderate or severe pain after the surgical removal of impacted third molars. Using a self-rating record, patients rated their pain and its relief hourly for up to 12 hours after medicating. Each active medication was significantly superior to placebo. The peak analgesic effect of fendosal 200 mg was similar to that of the aspirin 650-mg standard. Although fendosal's onset of action was slow (3 hours), its effect persisted for 8 hours, substantially longer than that of aspirin. Ibuprofen 400 mg was statistically significantly superior to aspirin 650 mg and fendosal 200 mg for most measures of peak and total analgesia, and its effect persisted for 8 hours. The results of this study raise some questions concerning the comparability of data from studies that employ different criteria for remedication and/or different criteria for the inclusion of data in the analyses of efficacy. Pharmacological management of pain for acute and chronic conditions has been guided by a scientific understanding of peripheral and central acting mechanisms for the control of inflammation as well as pain. Oral surgery pain is a reliable model to reference the effectiveness of commonly used analgesics such as ibuprofen and acetaminophen. A total of 706 patients who were experiencing moderate to severe pain received a single dose of ibuprofen, acetaminophen, or placebo. After 6 hours, the degree of pain relief and tolerance was assessed. Ibuprofen has important implications for postoperative pain in clinical practice. To determine the comparative efficacy of a new novel adenosine agonist (WAG 994) in postoperative pain after third molar surgery.
                One hundred and twenty-two patients with postoperative pain after third molar surgery were randomised in a placebo double-blind trial with an active control group. In the early postoperative period patients received either a single dose of WAG 994 1 mg, ibuprofen 400 mg or matched placebos. Pain intensity score was recorded on serial visual analogue scales over a 6 h investigation period. Similarly, pain relief was completed on a 4 point categorical scale at each evaluation point. Patients had access to escape analgesic and if these were taken, the time and dosage were recorded. A sparse sampling technique was used to investigate the relationship between analgesic effects and plasma concentrations of WAG 994.
                All three treatment groups were matched for various demographic variables. For all efficacy measures, WAG 994 was not significantly different from placebo (P >0.05), whereas ibuprofen 400 mg was significantly superior to placebo (P<0.001). No significant relationships (P<0.05) were found between WAG 994 pharmacokinetic variables and efficacy measures. Conclusion WAG 994, an adenosine agonist, did not show efficacy in the management of postoperative pain after third molar surgery. Although this pain responds well to nonsteroidal anti-inflammatory drugs, it appears to be resistant to compounds that interact with purinergic receptors. In a single-dose, double-blind, parallel-group, single-site study, ibuprofen lysine 200 mg (IBL 200) was compared with acetylsalicylic acid 500 mg (ASA 500) and placebo in 183 patients with moderate-to-severe postoperative dental pain. The relative onset of analgesic response, duration and degree of analgesia, and safety were assessed over a 6-hour postdose period. Analgesic efficacy was assessed by patient self-rating of pain intensity, pain relief, time to meaningful pain relief, global evaluation, and requirement for additional analgesic medication; both IBL 200 and ASA 500 were significantly more effective than placebo. IBL 200 also had a significantly faster onset of action, greater peak and overall analgesic effect, and longer duration of analgesia than ASA 500. All treatments were generally well tolerated. 1. Two separate placebo-controlled studies of parallel design were carried out to evaluate the efficacy of single doses (400 mg) of soluble ibuprofen, ibuprofen liquid in a gelatin capsule and ibuprofen tablets (Nurofen), in patients with postoperative pain after third molar surgery. 2. All ibuprofen preparations provided significant pain relief (P less than 0.05) over a 6 h investigation period. 3. Mean pain scores after ibuprofen tablets and ibuprofen liquid in a gelatin capsule were similar. 4. Soluble ibuprofen 400 mg provided an earlier onset of pain relief (20 min) than ibuprofen tablets (30 min). 5. No unwanted effects were reported in the various ibuprofen treatment groups. 6. The ibuprofen preparations evaluated in this study are effective up to 4 h for controlling postoperative pain after third molar surgery. The soluble form is more efficacious with regard to onset of action. Two hundred forty-one outpatients with postoperative pain after the surgical removal of impacted third molars were randomly assigned, on a double-blind basis, to receive a single oral dose of bromfenac 5, 10, or 25 mg, aspirin 650 mg, ibuprofen 400 mg, or placebo. Using a self-rating record, subjects rated their pain and its relief for 8 hours after medicating. Estimates of summed pain intensity difference, peak pain intensity difference, total relief, peak relief, and hours of 50% relief were derived from these subjective reports. All active treatments were significantly superior to placebo, and the slope of the dose-response curve for bromfenac was significant. Bromfenac 5 mg and aspirin 650 mg were equianalgesic; bromfenac 25 mg was slightly more efficacious than ibuprofen 400 mg. Bromfenac 25 mg and ibuprofen 400 mg were significantly superior to the other active treatments. Adverse effects were transient and consistent with the pharmacologic profiles of the medications evaluated. Our purpose was to compare the analgesic efficacy and safety of single oral doses of the combination of ibuprofen 400 mg plus codeine 60 mg and the combination of ibuprofen 200 mg plus codeine 30 mg with ibuprofen 400 mg alone, codeine sulfate 60 mg alone, and placebo. One hundred ninety-five patients with severe pain resulting from episiotomy, cesarean section, or gynecologic surgery completed a randomized, double-blind, stratified, parallel-group study. Patients were observed during a 4-hour period after medication. Based on the sum of the pain intensity differences (SPID), total pain relief (TOTPAR), and most of the hourly direct measures of pain and relief, both doses of the combination and ibuprofen 400 mg alone were statistically superior to placebo. Codeine 60 mg was statistically superior to placebo based on TOTPAR, the global ratings, and a few hourly measures. The mean effect of the combination of ibuprofen 400 mg plus codeine 60 mg was significantly superior to the mean effect of ibuprofen 400 mg alone 1/2, 1, and 2 hours after medication and to the mean effect of ibuprofen 400 mg alone and codeine 60 mg alone for SPID, TOTPAR, and other measures as well. The low-dose combination was significantly more effective than codeine 60 mg for a few hourly measures but was not significantly superior to ibuprofen 400 mg. Based on these findings it appears that the combination of ibuprofen 400 mg plus codeine 60 mg, particularly in the first few hours after medication, is more efficacious than its constituents. MK-0703 is a selective cyclooxygenase-2 inhibitor investigated for the treatment of acute pain and inflammation. The purpose of this single-dose, randomized, double-blind, double-dummy, placebo-controlled, parallel-group study was to compare MK-0703 12.5, 50, and 100 mg with ibuprofen 400 mg or placebo in patients who experienced moderate to severe pain after surgical removal of at least 2 third molars. Overall analgesic effect, duration of analgesic effect, time to onset of analgesic effect, peak analgesic effect, and tolerability were assessed over a 24-hour postdose period. The primary endpoint of this study was total pain relief over 8 hours postdose. The study included 121 patients (mean age, 23 yr); 16, 31, 28, 31, and 15 patients enrolled in the placebo, MK-0703 12.5 mg, MK-0703 50 mg, MK-0703 100 mg, and ibuprofen 400 mg groups, respectively. Both MK-0703 50 and 100 mg were significantly more effective than placebo for all endpoints (P < 0.01) and comparable with ibuprofen 400 mg. The onset of analgesic effect in the MK-0703 50 mg and 100 mg and ibuprofen 400 mg groups did not differ significantly from each other (P > 0.20). MK-0703 was generally well tolerated in single doses up to 100 mg. In summary, MK-0703 50 and 100 mg were efficacious in the treatment of postoperative dental pain and were indistinguishable from the active comparator, ibuprofen 400 mg. Intravenous flurbiprofen, a non-steroidal antiinflammatory drug (NSAID), has been used recently for postoperative pain relief in adults. The drug is also likely to have antiemetic property. The present study was undertaken to investigate the effect of flurbiprofen on postoperative pain and emesis in children undergoing strabismus surgery, which is well known to produce postoperative nausea and vomiting.
                In a prospective, randomised, controlled clinical trial, 90 children aged 2-11 yr received saline (control), flurbiprofen 0.5 mg.kg-1, or flurbiprofen 1 mg.kg-1. Saline and flurbiprofen were administered i.v. immediately after induction of anaesthesia. Anaesthesia was induced and maintained with sevoflurane and nitrous oxide in oxygen. Postoperative pain was assessed by a blinded observer using an objective pain scale (OPS). No opioids or antiemetics were administered throughout the study. The incidence and frequency of vomiting were compared among groups.
                Flurbiprofen 1 mg.kg-1 provided lower OPS (highest) scores during the eight hours after surgery and a reduced requirement for postoperative supplementary analgesic (diclofenac suppository) compared with the other two regimens. The two doses of flurbiprofen failed to decrease the incidence and frequency of vomiting.
                These data suggest that preoperative flurbiprofen 1 mg.kg-1 iv is a simple and effective approach to postoperative pain relief but not to the prevention of emesis following paediatric strabismus surgery. Combination analgesics may offer improved analgesic efficacy, particularly for moderate to severe pain.
                This study evaluated the analgesic benefits of concurrent ibuprofen and paracetamol compared with each drug used alone in the management of acute postoperative dental pain.
                Healthy patients aged 16 to 40 years undergoing surgical removal of 3 to 4 impacted molars (total impaction score > or = 9) were enrolled in this randomized, double-blind, placebo-controlled, parallel-group, single-dose, 2-center, modified factorial US study. Patients were randomly assigned in a ratio of 2:1:2:1:1 to ibuprofen 400 mg/paracetamol 1000 mg, ibuprofen 200 mg/paracetamol 500 mg, ibuprofen 400 mg, paracetamol 1000 mg, or placebo when postoperative pain reached moderate to severe intensity. The primary efficacy end point was the sum of pain relief and pain intensity differences from 0 to 8 hours (SPRID8). Several secondary end points were also measured, including total pain relief (TOTPAR), sum of pain intensity differences (SPID), and SPID on the visual analog scale (SPID VAS) at various time points. Other analgesic efficacy measures included peak effect, onset and duration of effect, and patients' overall assessment of treatment. The tolerability of study medications was assessed in terms of the frequency and nature of adverse events, which were assessed with standard questions, as well as changes from baseline in vital signs.
                A total of 234 patients were randomly assigned to treatment and included in the intent-to- treat population. The patients were predominantly female (74.4% [174/234]) and white (76.5% [179/234]); mean (SD) age was 20.8 (3.1) years and weight was 69.1 (16.5) kg. For SPRID8, the group treated with ibuprofen 400 mg/paracetamol 1000 mg had significantly better mean scores compared with ibuprofen alone (P < 0.001), paracetamol alone (P < 0.001), and ibuprofen 200 mg/paracetamol 500 mg (P = 0.02). The group taking ibuprofen 200 mg/paracetamol 500 mg achieved significantly better mean SPRID8 scores than paracetamol alone (P = 0.03), but not ibuprofen alone (P = NS). Ibuprofen 400 mg/paracetamol 1000 mg was associated with significantly better scores than was single-agent therapy for TOTPAR, SPID, and SPID VAS at all time intervals and for SPRID from 4 to 6 hours (all, P < 0.001). Pairwise comparisons found statistically significant differences in favor of all active treatments versus placebo for virtually all efficacy end points, thereby supporting assay sensitivity. Adverse events were similar across treatments; the most frequent were nausea (26.1% [61/234]), vomiting (18.8% [44/234]), headache (10.3% [24/234]), and dizziness (8.1% [19/234]).
                Concurrent ibuprofen and paracetamol appeared to provide significantly better analgesic efficacy compared with ibuprofen or paracetamol alone for acute postoperative dental pain in these adolescents and adults.
                Copyright 2010 Excerpta Medica Inc. All rights reserved. Several reports have suggested that preoperative nociceptive block may reduce postoperative pain, analgesic requirements, or both, beyond the anticipated duration of action of the analgesic agents. We have investigated, in a double-blind, placebo-controlled study, pre-emptive analgesia and the respiratory effects of preoperative administration of a multimodal antinociceptive regimen. Thirty patients undergoing thoracotomy were allocated randomly to two groups. Before surgery, the treatment group (n = 15) received morphine 0.15 mg kg-1 i.m. with perphenazine 0.03 mg kg-1 i.m. and a rectal suppository of indomethacin 100 mg, while the placebo group (n = 15) received midazolam 0.05 mg kg-1 i.m. and a placebo rectal suppository. After induction of anaesthesia, the treatment group received intercostal nerve block with 0.5% bupivacaine and adrenaline 1:200,000 (3 ml) in the interspace of the incision and in the two spaces above and two spaces below. The placebo group received identical injections but with normal saline only. The treatment group consumed significantly less morphine by patient-controlled analgesia in the first 6 h after operation, but the total dose of morphine consumed on days 2 and 3 after surgery was significantly greater in the treatment group. There were no differences between the groups in postoperative VAS scores (at rest or after movement), PaCO2 values or postoperative spirometry. However, pain thresholds to pressure applied at the side of the chest contralateral to the site of incision decreased significantly from preoperative values on days 1 and 2 after surgery in both groups. The results of this study do not support the preoperative use of this combined regimen for post-thoracotomy pain. Ibuprofen is a safe and effective analgesic, but some formulations have a slow onset of action. Ibuprofen arginate is a rapidly absorbed salt designed to promote more rapid onset of analgesia. A clinical trial was conducted in 226 patients with postoperative dental pain to assess the analgesic efficacy and speed of onset of the arginine salt of ibuprofen compared with one of the commercially available forms of ibuprofen. Patients were administered a single dose of either ibuprofen arginate (200 mg or 400 mg), ibuprofen (200 mg or 400 mg), or placebo in this double-blind, randomized trial. To determine the onset of action of the study medication patients were required to note time to "any" pain relief and then time to "meaningful" pain relief, using the two-stopwatch method. Pain intensity and relief were assessed using traditional categorical scales over a 6-h period. Meaningful pain relief was achieved in 42 min and 24 min for ibuprofen arginate 200 mg and 400 mg, respectively, compared with 50 min and 48 min for ibuprofen 200 mg and 400 mg, respectively ( P<0.05). The results for the measurements of analgesic effectiveness [sum of pain intensity difference, total pain relief (TOTPAR), peak pain relief and overall evaluation of treatment] all showed that both doses of ibuprofen arginate and both doses of ibuprofen were significantly better than placebo and both 200-mg and 400-mg ibuprofen arginate doses were significantly better than ibuprofen 200 mg for peak pain relief. Mean plasma ibuprofen concentrations at 30 min and 60 min, respectively, were: ibuprofen arginine 200 mg, 13.9 micro g/ml and 15.7 micro g/ml; ibuprofen arginine 400 mg, 29.5 micro g/ml and 29.3 micro g/ml; ibuprofen 200 mg 2.5 micro g/ml and 5 micro g/ml; ibuprofen 400 mg, 2.3 micro g/ml and 7.4 micro g/ml. ( P<0.05). Adverse event profiles were similar across treatment groups. These results overall suggest that ibuprofen arginate when taken at doses equivalent to commercially available ibuprofen formulations produces analgesia that is faster in onset. Two-hundred six outpatients with postoperative pain after the surgical removal of impacted third molars were randomly assigned on a double-blind basis to receive oral doses of ketorolac tromethamine 10 and 20 mg, ibuprofen 400 mg, acetaminophen 600 mg, a combination of acetaminophen 600 mg plus codeine 60 mg, or placebo. Using a self-rating record, subjects rated their pain and its relief hourly for 6 hours after medicating. All active medications were significantly superior to placebo. Analgesia was similar for ketorolac 10 and 20 mg and ibuprofen 400 mg; however, these treatments were superior to acetaminophen alone and the acetaminophen-codeine combination. The analgesic effect of each active medication was significant by hour 1 and persisted for 5-6 hours. The data suggest a plateau in ketorolac's analgesic efficacy at the 10-mg level. Repeat-dose data indicated that on the day of surgery ketorolac 10 and 20 mg and ibuprofen 400 mg were superior to acetaminophen 600 mg; ketorolac 20 mg was also superior to acetaminophen-codeine. Differences among active medications were not significant when data for the entire postoperative period (days 0-6) were evaluated. The frequency of adverse effects was similar for the active medications. Hydrocodone is a semisynthetic opioid with analgesic and antitussive properties qualitatively similar to other opioid agonists. Ibuprofen is a nonsteroidal antiinflammatory agent with analgesic and antipyretic activity and is an effective, primarily peripheral-acting antiinflammatory analgesic. The objective of this clinical trial was to determine the additive analgesic effect of the combination of 15 mg hydrocodone bitartrate with 400 mg ibuprofen, relative to 400 mg ibuprofen alone and placebo, in the treatment of postoperative pain. The single-dose analgesic efficacy of the combination of hydrocodone bitartrate with ibuprofen was compared with ibuprofen alone and placebo in 120 patients with moderate or severe postoperative pain after abdominal surgery. Analgesia was measured during the 6-hour period after dosing based on onset of relief, hourly and summary variables, and duration of effect. A significantly greater proportion of patients treated with the hydrocodone/ibuprofen combination reported onset of relief compared with ibuprofen or placebo; however, the distribution functions for time to onset of relief did not differ among treatments. Hydrocodone with ibuprofen and ibuprofen alone were significantly more effective than placebo for all measures of analgesia. The combination of hydrocodone with ibuprofen was significantly superior to ibuprofen for all hourly analgesic evaluations, weighted sum of pain intensity differences (SPID), total pain relief (TOTPAR), and global rating of study medication. No patients in the hydrocodone with ibuprofen group required analgesic remedication during the 6-hour study period, compared with 25% and 82% in the ibuprofen and placebo groups, respectively. The analgesic superiority of 15 mg hydrocodone bitartrate combined with 400 mg ibuprofen compared with 400 mg ibuprofen alone was demonstrated across many efficacy variables. The analgesic efficacy of 200 mg ibuprofen plus 30 mg codeine, 200 mg ibuprofen and placebo was investigated in a new analgesic evaluation model using single- and repeated-dose administration. The study was a double-blind randomized cross-over investigation in 26 coxarthrosis patients with persistent pain. After a washout period of at least 2 days with paracetamol available as rescue analgesic, each of the 3 treatments was administered in a total of 6 doses during 24 h. The hourly pain intensity was recorded on a 100-mm visual analogue scale (VAS) for 8 h after the 1st and the 6th dose. The pretreatment VAS score was 31-37 mm. After the 1st dose the 8-h mean pain intensity values were 25, 27, and 26 mm after ibuprofen plus codeine, ibuprofen, and placebo, respectively. Following another 5 doses every 4 h the corresponding values were 10, 17 and 29 mm. Repeated administration of both active drugs reduced the pain intensity significantly. The analgesic efficacy of ibuprofen plus codeine was significantly superior to that of ibuprofen which was, in turn, superior to that of placebo. In conclusion, analgesic efficacy was better differentiated after repeated-dose than after single-dose administration. The present study design was able to differentiate between 200 mg ibuprofen plus 30 mg codeine and 200 mg ibuprofen alone in a relatively small number of patients. To determine the relative analgesic efficacy of ibuprofen 400 mg and acetaminophen 1000 mg, we conducted a single-dose, double-blind, placebo-controlled, randomized clinical trial using a standard assay for analgesic agents, the dental pain model. At regular intervals over 6 hours, 184 patients who had undergone dental impaction surgery rated pain intensity and relief on categorical scales and pain half-gone on a dichotomous nominal scale; a categorical overall evaluation was completed at the end of 6 hours. Both active agents were effective compared to placebo. Ibuprofen 400 mg was more effective than acetaminophen 1000 mg for Sum Pain Intensity Difference (SPID), Total Pain Relief (TOTPAR), sum pain half-gone, and overall evaluation (P less than .05 to P less than .001). The time-effect curves demonstrated a greater peak effect and longer duration of action for ibuprofen 400 mg compared to acetaminophen 1000 mg. Side effects were reported in five ibuprofen patients, 11 acetaminophen-treated patients, and seven placebo patients. Based on the results of this clinical study, we conclude that ibuprofen 400 mg is a safe and more effective analgesic than acetaminophen 1000 mg for patients with acute pain. This randomised, double-blind study compared single dose lumiracoxib (a cyclooxygenase-2 selective inhibitor) 100 and 400 mg, ibuprofen 400 mg and placebo in patients with postoperative dental pain over 12 h. The primary efficacy variable was pain intensity difference. Lumiracoxib 400 mg and ibuprofen were superior to placebo from 1 to 12 h post dose while lumiracoxib 100 mg was superior from 1.5 to 9 h. Lumiracoxib 400 mg demonstrated the fastest median time to onset of analgesia (37.4 min) followed by ibuprofen (41.5), and lumiracoxib 100 mg (52.4; all p < or = 0.001 vs. placebo). Median time to rescue medication (h) was longer for lumiracoxib 400 mg (> or = 12), lumiracoxib 100 mg (approximately 7) and ibuprofen (approximately 8) than placebo (approximately 2; all p < or = 0.001 vs. placebo). Patients rated lumiracoxib 400 mg superior to the other active treatments (p < 0.05); lumiracoxib 100 mg was comparable with ibuprofen and superior to placebo (p < 0.001). Lumiracoxib provided rapid, effective and well-tolerated analgesia. The analgesic efficacy of single oral doses of drinkable diclofenac dispersible 50 mg was compared with that of ibuprofen 400 mg and placebo in a randomized, double-blind, parallel-group trial in 257 adult patients (245 valid for efficacy) with severe postoperative pain after extraction of an impacted lower third molar. In this study, pain intensity (on a 100-mm visual analog scale) and pain relief from baseline (using a five-point verbal rating scale) were assessed serially during an observation period of 6 hours. Intake of rescue analgesic was permitted in case of insufficient therapeutic effect; however at least 1 hour should have elapsed after test drug consumption. On the main efficacy variable, namely, reduction in the pain intensity score, both diclofenac dispersible (n = 83) and ibuprofen (n = 80) were statistically significantly (P < .01) superior to placebo (n = 82) starting at 20 and 40 minutes, respectively, after drug intake. The active medications were also significantly (P < .01) better than placebo for the secondary efficacy parameters viz. summed pain relief scores over 6 hours (TOTPAR-6); frequency of remedication with a rescue analgesic in the three treatment groups (diclofenac, 24%; ibuprofen, 28%; placebo, 65%); mean time to remedication; and global evaluation. All the treatments were well tolerated. Thus assay sensitivity of this trial (ibuprofen significantly better than placebo) has been demonstrated; in addition, diclofenac as a dispersible formulation has been shown to be an effective analgesic for the treatment of post-surgical dental pain. The combination of ibuprofen and paracetamol may confer analgesic benefits over monotherapy with either agent. In a previous study, an ibuprofen/paracetamol combination provided significantly better analgesic efficacy than comparable doses of ibuprofen or paracetamol alone in patients experiencing moderate to severe acute postoperative pain after extraction of impacted third molars.
                This study compared the efficacy and tolerability of 3 doses of a single-tablet fixed-dose combination (FDC) of ibuprofen and paracetamol (ibuprofen/paracetamol doses of 100 mg/250 mg, 200 mg/500 mg, and 400 mg/1000 mg) with comparable doses of ibuprofen (200 or 400 mg) monotherapy, paracetamol (500 or 1000 mg) monotherapy, and placebo in the 8 hours after surgical removal of 3 to 4 impacted third molars (stage 1) and with placebo over the next 72 hours (stage 2).
                This was a multicenter, 2-stage, randomized, double-blind, parallel-group, placebo-controlled, factorial study. Male or female outpatients were eligible for the study if they were aged >or=16 years, were referred for surgical removal of at least 3 impacted third molars (2 of which had to be mandibular impacted molars), and gave written informed consent. In stage 1, patients were randomly assigned to ibuprofen 200 mg, ibuprofen 400 mg, paracetamol 500 mg, paracetamol 1000 mg, FDC ibuprofen 100 mg/paracetamol 250 mg, FDC ibuprofen 200 mg/paracetamol 500 mg, FDC ibuprofen 400 mg/paracetamol 1000 mg, or placebo. In stage 2, patients who had been taking FDC therapy or placebo continued the same treatment, whereas those taking monotherapy received FDC therapy, incorporating the same dose of active monotherapy from stage 1. First-line rescue medication (hydrocodone 7.5 mg and paracetamol 500 mg) was available at any time after dosing; however, in stage 1, any patient who required rescue medication within 60 minutes of receipt of study medication was considered a "dropout" from therapy, and, in stage 2, patients who required >2 doses of first-line rescue medication in a 24-hour period were considered treatment failures. In stage 1, the primary efficacy end points were the sum of pain relief and pain intensity differences over an 8-hour follow-up period (SPRID8) and the pain relief and pain intensity difference scores at each time point (15, 30, 45, 60, 90, 120, 180, 240, 300, 360, 420, and 480 minutes after dosing). Several secondary variables were also measured, including the patient's global assessment of the study medication. The 2-stopwatch method was used for measures of perceptible and meaningful pain relief. In stage 2, the primary efficacy end point was the number of completed 24-hour periods (as 0, 1, 2, or 3) in which the patient required no more than one dose of rescue medication and rated the treatment as "good," "very good," or "excellent." The tolerability of study medications was assessed in relation to the frequency, nature, and severity of adverse events (AEs), as well as their relationship to study medication; vital signs were also measured. AEs were assessed at 8 hours after dosing in stage 1, at 72 hours after dosing in stage 2, and at the follow-up visit (7-10 days after surgery); in addition, patients were instructed to report any AE that occurred between scheduled assessments.
                Of 735 patients randomly assigned in stage 1, a total of 715 (97.3%) entered and 678 (92.2%) completed stage 2. Most patients were female (62.6% [460/735]) and white (91.3% [671/735]); the mean (SD) age was 20.3 (3.5) years and the mean weight was 69.7 (15.7) kg. The mean total impaction score was 11.1 (1.4), and the mean baseline pain score on the visual analog scale was 76.9 (12.0). Overall, 422 of 735 patients (57.4%) reported severe pain at baseline and 313 of 735 (42.6%) reported moderate pain. For the primary efficacy end point (SPRID8), FDC ibuprofen 400 mg/paracetamol 1000 mg was significantly more effective than ibuprofen 400 mg (P = 0.02) and paracetamol 1000 mg (P < 0.001) in the immediate postoperative period (stage 1), and FDC ibuprofen 200 mg/paracetamol 500 mg was significantly more effective than ibuprofen 200 mg (P < 0.001) and paracetamol 500 mg (P < 0.001). The FDC ibuprofen 200 mg/paracetamol 500 mg was also significantly more effective than paracetamol 1000 mg (P < 0.001), but failed to reach statistical significance in comparison with ibuprofen 400 mg. Continued postoperative therapy with all 3 FDCs on an as-needed basis was significantly more effective than placebo during the subsequent 72 hours (all, P < 0.001). During stage 1, rescue medication was required by 53 of 73 (72.6%), 29 of 75 (38.7%), 21 of 74 (28.4%), 56 of 76 (73.7%), and 51 of 74 (68.9%) patients in the placebo group and the ibuprofen 200-mg, ibuprofen 400-mg, paracetamol 500-mg, and paracetamol 1000-mg treatment groups, respectively. In the FDC treatment groups, the need for rescue medication included 27 of 71 (38.0%), 40 of 143 (28.0%), and 32 of 149 (21.5%) patients in the ibuprofen 100-mg/paracetamol 250-mg, ibuprofen 200-mg/paracetamol 500-mg, and ibuprofen 400-mg/paracetamol 1000-mg groups, respectively. The rates of treatment-related AEs between the first and second doses of study medication were significantly lower for FDC ibuprofen 400 mg/paracetamol 1000 mg (8/149 patients [5.4%]) than for placebo (14/73 [19.2%]; P < 0.01) and paracetamol 1000 mg (10/74 [13.5%]; P < 0.05); and also lower for FDC ibuprofen 200 mg/paracetamol 500 mg (9/143 [6.3%]) compared with ibuprofen 200 mg (12/75 [16.0%]; P < 0.05) and paracetamol 500 mg (17/76 [22.4%]; P < 0.001).
                FDC ibuprofen 200 mg/paracetamol 500 mg and ibuprofen 400 mg/paracetamol 1000 mg were significantly more effective in this population than were comparable doses of ibuprofen or paracetamol alone in moderate to severe acute dental pain and were significantly more effective than placebo in providing sustained pain relief. Previous data have suggested that rofecoxib, a cyclooxygenase (COX)-2-specific inhibitor, had analgesic effects similar to those of the nonsteroidal anti-inflammatory drugs when tested in the post-dental surgery pain model. The objective of this parallel-group, double-masked, randomized, placebo- and active comparator-controlled clinical trial was to assess more fully the analgesic efficacy of rofecoxib in the treatment of postoperative dental pain. After dental surgery, 151 patients (50.3% women; mean age, 18.3 years; 93.4% white) experiencing moderate-to-severe pain were to receive a single dose of placebo, rofecoxib 50 mg, or ibuprofen 400 mg. Analgesic efficacy was assessed for up to 24 hours postdose using self-administered questionnaires. Tolerability was assessed using spontaneous reports of adverse experiences, physical findings, and laboratory measurements. The results of this study demonstrated that rofecoxib 50 mg was more effective than placebo on all measures of analgesic efficacy. Rofecoxib 50 mg exhibited overall analgesic effects, onset of analgesia, and peak analgesic effects that were not significantly different from those of ibuprofen 400 mg, with a significantly longer duration of action (P < 0.05). We concluded that rofecoxib was efficacious in the treatment of postoperative dental pain and that COX-2-derived prostanoids play a role in treatment of the pain associated with dental surgery. Combination analgesia is often recommended for the relief of severe pain. This was a double-blind, 5-arm, parallel-group, placebo-controlled, randomised, single-dose study designed to compare the efficacy and tolerability of a novel single-tablet combination of ibuprofen and paracetamol with that of an ibuprofen/codeine combination, and a paracetamol/codeine combination, using the dental impaction pain model. Subjects with at least 3 impacted third molars and experiencing moderate to severe postoperative pain were randomised to receive: 1 or 2 tablets of a single-tablet combination of ibuprofen 200mg/paracetamol 500mg; 2 tablets of ibuprofen 200 mg/codeine 12.8mg; 2 tablets of paracetamol 500mg/codeine 15mg; or placebo. Results for the primary endpoint, the sum of the mean scores of pain relief combined with pain intensity differences over 12hours, demonstrated that 1 and 2 tablets of the single-tablet combination of ibuprofen/paracetamol were statistically significantly more efficacious than 2 tablets of placebo (P<0.0001) and paracetamol/codeine (P⩽0.0001); furthermore, 2 tablets offered significantly superior pain relief to ibuprofen/codeine (P=0.0001), and 1 tablet was found noninferior to this combination. Adverse events were uncommon during this study and treatment emergent adverse events were statistically significantly less frequent in the groups taking the ibuprofen/paracetamol combination compared with codeine combinations. In conclusion, 1 or 2 tablets of a single-tablet combination of ibuprofen 200mg/paracetamol 500mg provided highly effective analgesia that was comparable with, or superior to, other combination analgesics currently indicated for strong pain. A single-tablet combination of ibuprofen 200mg/paracetamol 500mg provides highly effective analgesia, comparable or superior to other combination analgesics indicated for strong pain.
                Copyright © 2011. Published by Elsevier B.V. Because of its enhanced pharmacokinetic characteristics, ibuprofen arginate might be expected to provide faster pain relief than standard ibuprofen formulations in patients experiencing acute pain.
                This study assessed the analgesic efficacy, speed of onset, and tolerability of ibuprofen arginate compared with a commercially available form of ibuprofen in patients with postoperative dental pain.
                Patients were randomized to receive ibuprofen arginate 200 or 400 mg, ibuprofen 200 or 400 mg, or placebo in this multicenter, double-blind, double-dummy, parallel-group trial. Patients were observed for 6 hours after administration of a single dose of study medication. A repeated-dose, open-label phase followed. Pain intensity and pain relief were measured using traditional verbal descriptor scales; onset of analgesia was assessed using 2 stopwatches to measure the time to achievement of specific pain relief criteria.
                A total of 498 patients (219 men, 279 women; mean age, 21.5 years) participated in this study. Baseline pain was moderate in 388 patients (78%) and severe in 110 patients (22%). Meaningful pain relief was reached after a median of 29 and 28 minutes with ibuprofen arginate 200 and 400 mg, respectively, and after 52 and 44 minutes with ibuprofen 200 and 400 mg, respectively (all, P < 0.05). The percentages of patients who achieved meaningful pain relief within the first hour after treatment were 77.6% and 83.7% for ibuprofen arginate 200 and 400 mg, respectively, 61.0% and 63.0% for ibuprofen 200 and 400 mg, respectively, and 39.8% for placebo. The differences between ibuprofen arginate and ibuprofen were statistically significant (both doses, P < 0.05). Significantly greater numbers of patients achieved meaningful pain relief with ibuprofen arginate 400 mg compared with placebo from 20 minutes through 6 hours and with ibuprofen arginate 200 mg from 30 minutes through 6 hours (P < 0.05). Compared with placebo, a greater number of patients achieved meaningful pain relief with ibuprofen 400 mg from 45 minutes through 6 hours; with ibuprofen 200 mg. the corresponding interval was from I through 6 hours. After the first hour, pain reduction was similar for the similar doses of the 2 ibuprofen preparations. Median remedication times with both doses of ibuprofen arginate were similar to those with both doses of ibuprofen, ranging from 4.0 to 5.2 hours. Adverse-event profiles were similar between the 2 active medications.
                Ibuprofen arginate was effective in this population of patients experiencing moderate to severe pain after surgical extraction of > or = 1 impacted third molar, with 16 to 24 minutes' faster time to meaningful pain relief than with ibuprofen. The 2 formulations had similar tolerability profiles. A single-dose, double-blind, randomized, parallel trial was conducted to compare the analgesic efficacy of oral ibuprofen (I) 100, 200, or 400 mg, aspirin (ASA) 650 mg, and placebo in moderate to severe pain after extraction of impacted teeth. Subjective, self-evaluated pain intensity and pain relief reports, hourly for 6 hours, were used as indexes of analgesic response. Data on 227 evaluable patients showed significant differences among the 4 active treatments and placebo (p less than 0.001) by most measurements of analgesia. Although no consistent, significant differences were observed among the active drugs, I 400 mg performed the best, followed by I 200 mg, ASA 650 mg, and I 100 mg. Remedication was required by 59% patients receiving I 400 mg, 67% taking I 200 mg, 73% taking ASA 650 mg, 74% taking I 100 mg, and 96% receiving placebo. Differences between I 400 mg and I 100 mg were significant for remedication data (p less than 0.05). Side effects were minor, infrequent, and not dose related. In this study, I 100 mg was distinctly superior to placebo and probably as effective as ASA 650 mg in relieving pain. Only a shallow dose response of ibuprofen was observed. The relief of post-episiotomy pain was investigated in three groups of women, ranked ASA 1 or 2, using either a single dose of 400 mg of ibuprofen (n = 31), or 1 g of paracetamol (n = 28) or placebo (n = 31). Pain intensity was assessed with a visual analogic scale, a verbal scale and pain relief scores after half an hour, 1, 2, 3, 4, 5 and 6 h. The day after treatment, patients rated the quality of pain relief, and were asked whether they wished to take again the same drug for the same type of pain. In the placebo and paracetamol groups, respectively 22 and 16 patients asked for usual treatment before the sixth hour, whereas only 5 did so in the ibuprofen group (p less than 0.001). Ibuprofen was more effective after one hour than either of the other two drugs, whatever the scale or parameter used. In the ibuprofen group, the lower pain score was observed at the third hour. At six hours, the pain score did not differ from that three hours earlier. On the day after treatment, 22 patients from the ibuprofen group considered pain relief to have been good or excellent, versus 8 and 5 in the paracetamol and placebo groups respectively (p less than 0.001). Similarly, 24 patients from the ibuprofen group would accept the same drug again for the same type of pain, as opposed to 8 and 5 from the paracetamol and placebo groups respectively (p less than 0.01). The only side-effect reported was abdominal pain in one patient (placebo group).(ABSTRACT TRUNCATED AT 250 WORDS) A double-blind study comparing parenteral morphine, 8 mg, with parenteral placebo and with oral fenoprofen, 200 mg, for the relief of postoperative pain following outpatient surgery was undertaken in 90 patients. The study drugs were administered within 2 hours of the operation and the Visual Analogue Scale was used to assess pain intensity. Patients given placebos showed minimal change in mean pain intensity, whereas patients who received morphine had significantly less pain at all assessment periods. Pain relief in patients who received fenoprofen was, for the first 2 hours, better than following placebo but not as good as following morphine, but thereafter, there was no significant difference between the morphine and fenoprofen and both were significantly better than placebo. It is concluded that oral analgesics may be a useful alternative to the traditional parenteral analgesics for outpatient surgery. Recent studies have demonstrated that caffeine acts as an analgesic adjuvant when combined with acetaminophen, aspirin, or their mixture. Our objective was to determine whether similar enhancement of analgesia could be demonstrated when caffeine is combined with ibuprofen. On a double-blind basis, a single oral dose of ibuprofen (50, 100, or 200 mg), a combination of ibuprofen, 100 mg, with caffeine, 100 mg, a combination of ibuprofen, 200 mg, with caffeine, 100 mg, or placebo was randomly assigned to 298 outpatients with postoperative pain after the surgical removal of impacted third molars. With a self-rating record, subjects rated their pain and its relief hourly for 8 hours. All active treatments were significantly superior to placebo, and the caffeine effect was significant for every measure of analgesia. Relative potency estimates indicated that the combination was 2.4 to 2.8 times as potent as ibuprofen alone. The combination also had a more rapid onset and longer duration of analgesic action. The analgesic adjuvancy of caffeine clearly extends to combinations with nonsteroidal anti-inflammatory drugs other than acetaminophen or aspirin. This study was conducted to evaluate the dose range of etoricoxib in acute pain using the postoperative dental pain model further.
                This double-blind, randomized controlled study evaluated etoricoxib (90 and 120 mg), ibuprofen (600 mg), and acetaminophen (600 mg/codeine) (60 mg, (A/C)) in patients aged ≥ 18 years with moderate or severe pain after surgical extraction of ≥ 2 third molars (≥ 1 impacted). The patients reported pain intensity and pain relief over 24 hours. The primary efficacy endpoint was total pain relief over 6 hours (TOPAR6). Adverse events were evaluated throughout the study.
                There were 588 patients randomized to placebo (n=46),etoricoxib (90 mg (n=191)), etoricoxib (120 mg (n=97)), ibuprofen(2400 mg (n=192)), and A/C (n=62). The overall analgesic effect (TOPAR6) of etoricoxib (90, 120 mg) was significantly greater than that of placebo (P ≤ 0.001), and not inferior to that of ibuprofen; no discernible difference was observed between etoricoxib 90 and 120 mg. Both etoricoxib doses were superior to A/C (P ≤ 0.001). Etoricoxib (90 and 120 mg) and ibuprofen(2400 mg) were generally well tolerated and had a similar incidence of adverse events (AEs). A/C was associated with significantly more AEs that led to discontinuation (ie, nausea and vomiting).
                Etoricoxib (90 and 120 mg) showed similar efficacy in the postoperative dental pain model, which was noninferior to ibuprofen and superior to A/C. A higher number of tooth extractions or a higher mean impaction score may have led to a greater separation in efficacy between the 2 etoricoxib doses. Ibuprofen liquigel is a solubilized potassium ibuprofen 200-mg gelatin capsule formulation that was approved for over-the-counter use in 1995.
                This study compared the analgesic efficacy and tolerability of ibuprofen liquigel 200 mg, ibuprofen liquigel 400 mg, acetaminophen caplets 1000 mg, and placebo in patients experiencing moderate or severe pain after surgical removal of impacted third molars.
                This randomized, double-blind, parallel-group, 6-hour study was conducted in 210 patients experiencing moderate or severe postoperative pain. Ratings of pain intensity and pain relief were recorded every 15 minutes for the first hour, at 90 and 120 minutes, and then hourly through hour 6. The onsets of first perceptible relief and meaningful relief were recorded using 2 stopwatches. An analysis of variance model was employed to test for significant differences (P < or = 0.05) between treatment groups with respect to pain relief, pain intensity difference, total pain relief (TOTPAR), and summed pain intensity difference (SPID). Stopwatch measures were analyzed using the Cox proportional hazards model. Drug tolerability was assessed by monitoring the occurrence of adverse events.
                During the first 2 hours of the study (TOTPAR 2 and SPID 2), all active treatments were significantly more efficacious than placebo (P < 0.001), with ibuprofen liquigel 200 and 400 mg significantly more efficacious than acetaminophen 1000 mg (P < 0.05 and P < 0.01, respectively). For the entire duration of the study (TOTPAR 6 and SPID 6), only the 2 doses of ibuprofen liquigel were significantly more efficacious than placebo (P < 0.001). Ibuprofen liquigel 200 and 400 mg were also significantly more efficacious than acetaminophen 1000 mg on the summary measures TOTPAR 6 and SPID 6 (P < 0.01 and P < 0.001, respectively). Analysis of the stopwatch data revealed that all active treatments displayed significantly more rapid onsets to confirmed first perceptible relief (P < 0.001 to < 0.05) and meaningful relief (P < 0.001 to < 0.01) than did placebo, with ibuprofen liquigel 400 mg displaying a significantly more rapid onset to meaningful relief than acetaminophen 1000 mg (P < 0.05) and a significantly more rapid onset to confirmed first perceptible relief than acetaminophen 1000 mg (P < 0.001) and ibuprofen liquigel 200 mg (P < 0.01). All adverse events were considered mild or moderate, with an overall incidence of 11.5% in the ibuprofen liquigel 200-mg group, 6.8% in the ibuprofen liquigel 400-mg group, 19.0% in the acetaminophen 1000-mg group, and 25.9% in the placebo group.
                Ibuprofen liquigel provided greater peak and overall analgesic effects and a more rapid onset to analgesia than did acetaminophen 1000 mg. The objective of this single dose, double-blind study was to determine the relative analgesic efficacy of low-dose ketoprofen (6.25 mg, 12.5 mg, and 25 mg) compared with ibuprofen (200 mg) and placebo in 175 patients with moderate to severe postoperative pain secondary to extraction of impacted third molars. Analgesia was measured during the 6-hour period after administration based on onset of relief, hourly and summary variables, and duration of treatment effect. All active treatments were significantly more effective than placebo for many hourly measures and for the summary measures sum of pain intensity differences (SPID), sum of hourly pain relief values (TOTPAR), time to peak pain relief, and patient global assessment of study medication. The three ketoprofen doses were significantly more effective than placebo beginning at 30 minutes, whereas ibuprofen was significantly better than placebo beginning at 1 hour. A dose-response relationship was observed for ketoprofen, with the two higher doses providing significantly greater analgesia than the lower dose. However, a plateau effect was seen between the 12.5-mg and 25-mg dose levels. A significantly greater proportion of patients treated with each of the active treatments (ranging from 0.83 to 0.88) reported onset of relief compared with placebo (0.20). The distribution functions of onset of relief differed significantly among treatments, with ketoprofen 12.5 mg and 25 mg having a faster onset than ibuprofen 200 mg and ketoprofen 6.25 mg. The duration of effect was generally shorter for ketoprofen than for ibuprofen, and these difference were significant. This study provides evidence that at the dose levels of 12.5 mg and 25 mg, ketoprofen is an effective analgesic in providing relief of postoperative dental pain. Ketoprofen 12.5 mg and 25 mg provide significantly greater relief in the earlier time period, with a faster onset and shorter duration of effect than ibuprofen 200 mg. The two higher doses of ketoprofen provided similar analgesia, and no additional benefit was obtained by increasing the dose of ketoprofen to 25 mg. Therefore, we conclude that ketoprofen 12.5 mg is an appropriate dose for over-the-counter use. We have compared single oral doses of drinkable diclofenac dispersible (50 mg) with ibuprofen (400 mg) and placebo in a randomized, double-blind, parallel-group trial in 127 adults complaining of at least moderately severe pain after removal of an impacted third molar. Within 40 min both diclofenac and ibuprofen produced significant pain relief that persisted for 6 h. There were no differences between diclofenac and ibuprofen in analgesic efficacy. A combination of 20 mg codeine base and ibuprofen 400 mg was compared with ibuprofen 400 mg in a randomised double-blind cross-over study of multiple doses in 25 patients after 2-stage bilateral third molar removal. The combination produced significantly greater pain relief and doubled the hours of minimum pain intensity and maximal relief on the day of surgery. The patients rated the combination significantly better than ibuprofen alone, and the combination was preferred by 16 of the 22 patients expressing a preference. There was no significant increase in side-effect incidence with the combination. The 30% increase in analgesic effect may be of clinical benefit, and this trial design, cross-over with multiple dosing in out-patients, may be a sensitive test for analgesics, potentially more predictive of side-effect problems than single-dose studies. Two randomized, double-blind, parallel-group single-dose 2 x 2 factorial analgesic studies compared a single-dose or a 2-tablet dose of a combination of 7.5 mg hydrocodone bitartrate with 200 mg ibuprofen with each constituent alone and with a placebo in women with moderate or severe postoperative pain from abdominal or gynecologic surgery. A nurse-observer recorded patient reports of pain intensity and pain relief periodically for 8 hours. In both studies, the combination was significantly superior to placebo for sum of the pain intensity differences (SPID), total pain relief (TOTPAR), peak pain intensity difference (PID) and pain relief, global evaluation, and time to remedication. The combination was likewise significantly superior to both hydrocodone and ibuprofen for most of these summary measures of analgesia. In a factorial analysis, both the hydrocodone and ibuprofen effects were significant for most summary measures of analgesia, whereas results of the interaction contrast were consistent with the concept that the analgesic effect of the combination represents the additive analgesia of its 2 constituents. The optimal short-term, symptomatic therapy for osteoarthritis of the knee has not been fully determined. Accordingly, we compared the efficacy of a nonsteroidal antiinflammatory drug, ibuprofen, given in either an antiinflammatory dose (high dose) or an analgesic dose (low dose), with that of acetaminophen, a pure analgesic.
                In a randomized, double-blind trial, 184 patients with chronic knee pain due to osteoarthritis were given either 2400 or 1200 mg of ibuprofen per day or 4000 mg of acetaminophen per day. They were evaluated after a washout period of three to seven days before the beginning of the study, and again after four weeks of treatment. The major measures of outcome included scores on the pain and disability scales of the Stanford Health Assessment Questionnaire (range of possible scores, 0 to 3), scores on the visual-analogue scales for pain at rest and pain while walking, the time needed to walk 50 ft (15 m), and the physician's global assessment of the patient's arthritis.
                Seventy-eight percent of the patients completed four weeks of therapy. No significant differences were noted among the three treatment groups with respect to failure to complete the trial because of noncompliance or adverse events. All three groups had improvement in all major outcome variables, and the groups did not differ significantly in the magnitude of improvement in most variables. The mean improvement (change) in the scores on the pain scale of the Health Assessment Questionnaire was 0.33 with acetaminophen (95 percent confidence interval, 0.14 to 0.52), 0.30 with the low dose of ibuprofen (95 percent confidence interval, 0.09 to 0.51), and 0.35 with the high dose of ibuprofen (95 percent confidence interval, 0.13 to 0.57). Side effects were minor and similar in all three groups.
                In short-term, symptomatic treatment of osteoarthritis of the knee, the efficacy of acetaminophen was similar to that of ibuprofen, whether the latter was administered in an analgesic or an antiinflammatory dose. Ibuprofen, 400 mg, was compared with 300 mg acetaminophen plus 30 mg of codeine and placebo in 120 post-orthopedic surgery patients with moderate to severe pain. The study was designed as a double-blind, single-dose, parallel-group analgesic efficacy assay. Estimates of analgesia were obtained up to 6 h using categorical and visual analog measures of pain intensity and pain relief. Estimates of selected elements of mood and of sensory and affective components of pain were obtained at 0 and 2 h using contrasting mood word/phrase pairs and a portion of the McGill Pain Questionnaire, respectively. Drugs were distinguishable from placebo in total analgesic effect, and ibuprofen was more effective than acetaminophen plus codeine, especially in terms of duration. While peak effects were comparable, they occurred 1 h later following ibuprofen. Differences among treatments were more discernible using visual analog measures. Side effects were minimal. Ibuprofen provided greater improvement in selected elements of mood than acetaminophen plus codeine at comparable levels of pain relief. While decreases in the sensory component of pain were most highly associated with pain relief provided by ibuprofen, decreases in the affective component were most highly associated with pain relief following acetaminophen plus codeine. These latter results indicate that mood assessment and the discrimination between sensory and affective components of pain could be particularly useful within analgesic drug assays, especially when comparing analgesics of differing pharmacologic class and when comparing the results of such assays in pain syndromes characterized by differing pain quality. To compare the analgesic and side effects of preemptively used epidural ketamine +bupivacaine, neostigmine +bupivacaine, and bupivacaine alone on postoperative analgesia after major abdominal surgery.
                Randomized, controlled study.
                Inpatient anesthesia at the department of surgery of a metropolitan hospital.
                30 ASA physical status I, II, and III patients scheduled for abdominal surgery.
                Group K received 1 mL (50 mg) ketamine and 5 mL (25 mg) bupivacaine epidurally, Group N received 1 mL (0.5 mg) neostigmine and 5 mL (25 mg) bupivacaine epidurally, and Group B received 1 mL saline and 5 mL (25 mg) bupivacaine epidurally 30 minutes before operation. All patients underwent anesthesia induction with thiopental and vecuronium; anesthesia was maintained with isoflorane and vecuronium. For postoperative analgesia, all patients received epidural morphine for 48 hours postoperatively.
                Standard monitoring included: 48 hours of analgesic requirement, visual analog scale (VAS), mean arterial pressure (MAP), and heart rate (HR) in the 1st, 2nd, 6th, 12th, 24th, and 48th hours. Data were analyzed using Kruskall-Wallis and Mann Whitney U tests, with a p < 0.05 considered statistically significant. No significant differences were observed regarding MAP and HR among the groups during the study period. In Group N, VAS was significantly lower than Group K and Group B. The total opioid consumption in Group N was significantly lower than in Groups K and B in the first 48 hours after the operation.
                Preemptive neostigmine can be a good choice for postoperative analgesia. Peripheral nociceptive barrage after tissue injury results in acute pain and a variety of physiologic responses, including pituitary secretion of beta-endorphin. This study evaluated whether administration of the pharmacologically active S(+)-isomer of ibuprofen suppresses acute pain and plasma beta-endorphin levels in the oral surgery model of acute pain.
                Subjects in a single-dose, double-blind, parallel-group study received either 200 mg S(+)-ibuprofen, 400 mg S(+)-ibuprofen, 400 mg racemic ibuprofen, or placebo. Both doses of S(+)-ibuprofen resulted in significantly greater analgesia over the first 60 minutes in comparison to racemic ibuprofen and placebo; the 400 mg dose of S(+)-ibuprofen also produced greater analgesia at 2 and 3 hours. Plasma levels of immunoreactive beta-endorphin decreased over time coincident with the onset of analgesia in all groups but were significantly less than placebo after both doses of S(+)-ibuprofen from 30 to 120 minutes.
                These findings show that, compared with racemic ibuprofen, administration of the S(+)-isomer of ibuprofen results in faster analgesic onset, greater peak analgesia, similar duration of action, and a low incidence of adverse effects, while suppressing nociceptive activation of the pituitary-adrenal axis. The objectives were to compare the relative merits of ibuprofen 400 mg and dihydrocodeine 30 mg or 60 mg taken up to four times daily for up to 6 days in the treatment of pain after third molar removal. A randomised, double-blind, multiple dose, crossover study was undertaken in 68 patients undergoing two-stage bilateral lower third molar removal. The results showed that ibuprofen produced significantly greater analgesia than either of the dihydrocodeine treatments on the day of surgery. Ibuprofen and dihydrocodeine 60 mg produced significantly greater analgesia than dihydrocodeine 30 mg on the day after surgery, and on days 4 and 5 ibuprofen was again significantly superior to dihydrocodeine 60 mg. Roughly half the patients taking dihydrocodeine stopped the study on the day after surgery, because of adverse effects and/or inadequate relief, compared with 6 out of 44 taking ibuprofen. Dihydrocodeine 60 mg produced four times the number of patients affected by adverse effects compared with ibuprofen, and dihydrocodeine 30 mg three times as many. The principal adverse effects were nausea, vomiting and drowsiness. In conclusion, ibuprofen produced better analgesia than dihydrocodeine with significantly fewer adverse effects and is therefore a better choice for pain relief after oral surgery. Non-steroidal anti-inflammatory drugs (NSAIDs) are used as analgesic in postoperative pain to reduce opioid side effects, such as drowsiness and nausea. However, NSAIDs have not been used extensively in cardiac surgical patients due to the fear of untoward effects on gastric, renal, and coagulation parameters. This study will evaluate the efficacy and safety of three NSAIDs for pain control in CABG patients.
                One hundred and twenty patients scheduled for elective CABG surgery were enrolled in randomized, double blind, controlled study. Standardized fast track cardiac anesthesia was used. One dose of drug (75 mg diclofenac, 100 mg ketoprofen, 100 mg indomethacin, or placebo) was given pr one hour before tracheal extubation and a second dose 12 hr later. Pain was treated with morphine iv and acetaminophen po. Visual analogue pain scores were recorded at baseline, 3, 6, 12 and 24 hr after the first dose of drug.
                There were no differences among the groups in pain scores. Only patients who received diclofenac required less morphine than patients in the control group (P < 0.05). When the total amounts of pain medications were computed to morphine equivalents, only patients in the diclofenac group received less pain medications than the placebo group (P < 0.05). Proportion of patients with postoperative increase of creatinine level (20% and over) did not differ between placebo and drug groups.
                Non-steroidal anti-inflammatory drugs may be used for analgesia management post CABG surgery in selected patients. Diclofenac appears to have the best analgesic effects by reducing the morphine and other analgesic requirement postoperatively. Our purpose was to evaluate the analgesic efficacy and safety of single oral doses of flurbiprofen 25, 50 and 100 mg, aspirin 600 mg, and placebo in the relief of moderate to severe post-episiotomy pain. One hundred and fifty-two evaluable patients completed a randomized, double-blind, stratified, parallel groups study. They were observed over a six hour period by one nurse-observer. Based upon each of the summary efficacy measures SPID, TOTAL and PEAK % and most of the hourly direct measures of pain intensity and pain relief, each of the four active treatments were statistically superior to placebo. Flurbiprofen 25 mg appeared to be slightly less effective than aspirin 600 mg, but the differences were not statistically significant. Flurbiprofen 50 and 100 mg were quite similar and were significantly more effective than aspirin 600 mg and flurbiprofen 25 mg. There were no observed or reported adverse effects. One hundred sixty-four outpatients with postoperative pain after the removal of impacted third molars were randomly assigned on a double-blind basis, to receive oral doses of flurbiprofen 25, 50, or 100 mg; aspirin 600 mg; or placebo. Using a self-rating record, subjects rated their pain and its relief hourly for 8 hours after medicating. Estimates of sum of pain differences (SPID), peak pain intensity difference (PID), total relief, peak relief, and hours of 50% relief were derived from these subjective reports. All active medications were significantly superior to placebo. Analgesia was similar for flurbiprofen 25 mg and aspirin 600 mg. Flurbiprofen 50 and 100 mg were significantly superior to aspirin for every measure of analgesia except peak PID. There was a significant dose-response regression between flurbiprofen 25 mg and both of the higher dosages. Flurbiprofen 50 and 100 mg did not differ significantly, suggesting a plateau in flurbiprofen's analgesia. The analgesic effect of flurbiprofen was significant by hour 1 and persisted for 8 hours. The frequency of adverse effects was similar for the active medications. To compare the relative merits of single doses of ibuprofen and ibuprofen plus caffeine in the treatment of pain after third molar removal.
                Randomised, double-blind, placebo-controlled, single-dose parallel-group comparison of placebo, ibuprofen 200 and 400 mg with ibuprofen 200 mg plus 50, 100 or 200 mg of caffeine.
                161 patients undergoing lower third molar removal.
                All active treatments produced significant analgesia and mood elevation compared with placebo. There was no significant difference in the effects of 200 and 400 mg of ibuprofen. Adding caffeine to 200 mg ibuprofen produced significantly more analgesic effect at 45 and 60 min than ibuprofen 200 mg alone. Ten patients reported 11 adverse effects, none in the highest caffeine dose group.
                Caffeine increased the analgesic effect of ibuprofen 200 mg, through an earlier onset of analgesic effect. This was achieved in this single dose context without problematic adverse effects. To investigate the effect of preoperative ibuprofen administration on renal function during and after infrarenal aortic surgery under thoracolumbar epidural anaesthesia (EPA).
                A prospective randomised, double-blinded clinical study.
                Operation room and intensive care unit in a university hospital.
                Twenty-six consecutive patients scheduled for elective infrarenal aortic surgery.
                The patients were prospectively randomised to receive 400 mg ibuprofen intravenously (i.v.) or a placebo aliquot before surgery.
                We assessed renal function by calculating creatinine clearance, and fractional sodium excretion before surgery (baseline), 1 h after cross-clamping (intraoperative), 6 h after cross-clamping (postoperative) and 24 h after cross-clamping (on the 1 st postoperative day). At each point in time, we additionally registered haemodynamics and determined the plasma concentration of 6-keto-PGF1alpha (stable metabolite of prostacyclin, PGI2), bicyclic PGE2 (stable metabolite of PGE1 E2), active renin, aldosterone and vasopressin by radioimmunoassays. Throughout the observation period the renal function parameters mostly remained within the normal range without a significant difference between ibuprofen- and placebo-treated patients (creatinine clearance: baseline 41 +/- 3 vs 38 +/- 6, intraoperative 57 +/- 8 vs 64 +/- 11, postoperative 64 +/- 9 vs 56 +/- 9, first postoperative day 43 +/- 5 vs 47 +/- 6 ml x min x m(-2), means +/- SEM). The plasma levels of 6-keto-PGF1alpha (68 +/- 8 vs 380 +/- 71* ng x l(-1)), bicyclic PGE2 (57 +/- 5 vs 88 +/- 9* ng x l(-1)) and vasopressin (14 +/- 7 vs 45 +/- 10* ng x l(-1), p < 0.0125), however, were significantly higher during the intraoperative period in the placebo-treated patients.
                The inhibition of endogenous prostaglandin release by ibuprofen does not substantially impair renal function during infrarenal aortic surgery under EPA. 1) To verify the usefulness of ketorolac administration (30 mg i.v.) before a surgical operation in terms of postoperative analgesia improvement; 2) To evaluate the impact of preoperative ketorolac administration on perioperative renal function and on intraoperative water balance; 3) to evaluate the presence of adverse effect due to preoperative NSAID use.
                Prospective randomized trial.
                University surgical department.
                Forty adult patients undergoing major abdominal surgery, randomized in 2 groups: in group 1 ketorolac (30 mg i.v.) was administered immediately after the induction and, for postoperative analgesia, ketorolac (30 mg i.v.) was administered beginning at the time of skin closure; in group 2 no ketorolac was administered before the operation and postoperative treatment was the same. Buprenorphine (0.3 mg i.m.) was administered in case of unsatisfactory analgesia. Fluids infused and diuresis were measured intraoperatively. One, 6 and 24 hours after the end of operation pain was evaluated using pain intensity score and VAS. The day after the operation serum creatinine and urea were measured.
                No statistically significant differences were found between groups regarding fluids infused, intraoperative diuresis, postoperative pain, adverse effects and number of bleeding episodes. More than 50% of patients, in either groups, required opioids administration.
                Ketorolac (30 mg i.v.) administration before a major abdominal operation does not improve postoperative analgesia nor determines significant alterations in renal function or increase in the frequency of abnormal bleedings. Opiate administration is necessary in more than 50% of the patients to achieve adequate analgesia. To compare the analgesic efficacy of single and multiple doses of ibuprofen with that of paracetamol in patients with knee or hip osteoarthritis (IPSO study).
                222 patients were randomised in a double blind, multicentre study-156 (70%) had a painful knee joint and 66 (30%) a painful hip joint. The main efficacy criterion was pain intensity assessment after a single dose (ibuprofen 400 mg, paracetamol 1000 mg). Functional disability assessment and patient global assessment were carried out over 14 days.
                The sum of the pain intensity difference over 6 hours after the first administration was significantly higher (p = 0.046) in the ibuprofen group than in the paracetamol group. Over 14 days pain intensity decreased from the first day and was significantly lower in the ibuprofen group than in the paracetamol group (p<0.05). The functional disability of the patient was assessed using the WOMAC; the ibuprofen group improved significantly over 2 weeks compared with the paracetamol group for each of the subscales: stiffness (p<0.002), pain (p<0.001), physical function (p<0.002). The drugs were equally safe.
                The IPSO study shows that for the treatment of osteoarthritic pain, ibuprofen 400 mg at a single and multiple dose (1200 mg/day) for 14 days is more effective than paracetamol, either as a single dose of 1000 mg or a multiple dose (3000 mg/day). Because ibuprofen and paracetamol have similar tolerability, this study indicates that the efficacy/tolerability ratio of ibuprofen is better than that of paracetamol in this indication over 14 days. The purpose of this study was to evaluate the contribution of endogenous opiates to the analgesic response after treatment with placebo, codeine, and ibuprofen after oral surgery. Eighty-one patients undergoing complicated dental extractions were pretreated with either a placebo or the narcotic antagonist naltrexone 50 mg, 30 minutes before surgery. After surgery, patients self administered one of three possible postsurgical medications, which included placebo, codeine 60 mg, and ibuprofen 400 mg, when their pain reached a moderate or severe intensity. The study was double-blind with the three postsurgical treatments being randomly allocated within each presurgical treatment block. Pain intensity, pain relief, pain half gone, and overall evaluations were assessed for up to 6 hours. Ibuprofen was significantly more efficacious (p < .05) than codeine or placebo for most analgesic measures. The administration of naltrexone before surgery reduced the analgesic response to both placebo and codeine. Pretreatment with naltrexone did not diminish the peak analgesic response to ibuprofen, but surprisingly prolonged (p < .05) the duration of its action. The results suggest that a blockade of endogenous opiates by naltrexone diminished the placebo response, but that naltrexone may prolong ibuprofen analgesia by some unknown mechanism.
The very substantial amount of high quality evidence demonstrates that ibuprofen is an effective analgesic in treating postoperative pain. NNTs for 200 mg and 400 mg ibuprofen did not change significantly from the previous review even when a substantial amount of new information was added. New information is provided on remedication.