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document
Circadian changes in the pharmacokinetics of oral ketoprofen . Several investigations which have taken treatment time into account have shown that the pharmacokinetic parameters , the therapeutic efficacy and even the toxicity of a large number of products may vary according to the administration schedule . The present study was carried out in order to evaluate any circadian changes in pharmacokinetic parameters of ketoprofen , a new non-steroidal anti-inflammatory drug ( NSAID ) . This randomised crossover study consisted of a single oral dose of ketoprofen 100mg administered to 8 healthy male volunteers , mean age 27.2 years , at 07.00 hours , 13.00 hours , 19.00 hours or 01.00 hours in 4 study periods during the first 3 months of the year . The order of administration was randomised , with each subject acting as his own control . A total of 14 blood and 4 urine samples were taken over a 12-hour period . The peak plasma concentration was twice as high after drug administration at 07.00 hours ( 13.4 +/- 1 mg/L ) than after other administration times ( 13.00 hours : 6.9 +/- 1 ; 19.00 hours : 7.2 +/- 0.7 ; 01.00 hours : 6.3 +/- 0.5 mg/L ) [ p less than 0.001 ] . The time to reach peak concentration was much longer after drug administration at 01.00 hours ( 135 +/- 16.7 min ) than at 07.00 ( 73.1 +/- 14.1 min ) , 13.00 ( 75 +/- 16.5 min ) or 19.00 hours ( 82.5 +/- 12.7 min ) [ p less than 0.05 ] . The lag time was significantly longer at 01.00 hours than at 13.00 hours ( p less than 0.01 ) . The absorption rate constant after treatment at 01.00 hours was less than at the other times of administration ( p less than 0.05 ) . The bodyweight-corrected area under the curve ( AUC0-12 ) was greater after 07.00 hours than after 13.00 ( p less than 0.01 ) or 19.00 hours ( p less than 0.05 ) and greater after 01.00 hours than after 13.00 hours ( p less than 0.05 ) . The elimination half-life was significantly longer after administration at 01.00 hours than after 19.00 hours ( p less than 0.05 ) , while the total clearance was lowest at 07.00 hours . Cosinor analysis demonstrated statistically significant circadian rhythms for all pharmacokinetic parameters described above . The amount of ketoprofen eliminated in the urine was delayed , and was significantly greater after the administration at 01.00 hours than 07.00 hours or 19.00 hours ( p less than 0.01 ) . The relationship between absorption , diffusion and/or elimination mechanisms of the drug are discussed .
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Intervention_Pharmacological
ketoprofen
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Intervention_Pharmacological
ketoprofen
76469
Intervention_Pharmacological
ketoprofen
76470
Intervention_Pharmacological
ketoprofen
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Outcome_Physical
pharmacokinetics
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Outcome_Other
therapeutic efficacy
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Outcome_Adverse-effects
toxicity
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Outcome_Physical
peak plasma concentration
76475
Outcome_Physical
time to reach peak concentration
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Outcome_Other
lag time
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Outcome_Physical
absorption rate
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Outcome_Physical
bodyweight-corrected area under the curve ( AUC0-12 )
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Outcome_Physical
elimination half-life
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Outcome_Other
total clearance
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Outcome_Physical
circadian rhythms
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Participant_Sample-size
8
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Participant_Condition
healthy
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Participant_Sex
male
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Participant_Age
27.2