87738
document
Serum bactericidal activities and comparative pharmacokinetics of meropenem and imipenem-cilastatin . The pharmacokinetics and serum bactericidal activities ( SBAs ) of imipenem and meropenem were investigated in a randomized crossover study . Twelve healthy male volunteers received a constant 30-min infusion of either 1 g of imipenem plus 1 g of cilastatin or 1 g of meropenem . The concentrations of the drugs in serum and urine were determined by bioassay and high-pressure liquid chromatography . Pharmacokinetic parameters were based on an open two-compartment model and a noncompartmental technique . At the end of infusion , the mean concentrations of imipenem and meropenem measured in serum were 61.2 +/- 9.8 and 51.6 +/- 6.5 mg/liter , respectively ; urinary recoveries were 48.6 % +/- 8.2 % and 60.0 % +/- 6.5 % of the dose in 12 h , respectively ; and the areas under the concentration-time curve from time zero to infinity were 96.1 +/- 14.4 and 70.5 +/- 10.3 mg.h/liter , respectively ( P < or = 0.02 ) . Imipenem had a mean half-life of 66.7 +/- 10.4 min ; that of meropenem was 64.4 +/- 6.9 min . The volumes of distribution at steady state of imipenem and meropenem were 15.3 +/- 3.3 and 18.6 +/- 3.0 liters/70 kg , respectively , and the mean renal clearances per 1.73 m2 were 85.6 +/- 17.6 and 144.6 +/- 26.0 ml/min , respectively . Both antibiotics were well tolerated in this single-dose administration study . The SBAs were measured by the microdilution method of Reller and Stratton ( L. B. Reller and C. W. Stratton , J. Infect . Dis . 136:196-204 , 1977 ) against 40 clinically isolated strains . Mean reciprocal bactericidal titers were measured 1 and 6 h after administration . After 1 and 6 h the median SBAs for imipenem and meropenem , were 409 and 34.9 and 97.9 and 5.8 , respectively , against Staphylococcus aureus , 19.9 and 4.4 and 19.4 and 4.8 , respectively , against Pseudomonas aeruginosa , 34.3 and 2.2 and 232 and 15.5 , respectively , against Enterobacter cloacae , and 13.4 and 2.25 and 90.7 and 7.9 , respectively , against Proteus mirabilis . Both drugs had rather short biological elimination half-lives and a predominantly renal route of elimination . Both carbapenems revealed high SBAs against clinically important pathogens at 1 h ; meropenem had a higher SBA against E. cloacae and P. mirabilis , and the SBA of imipenem against S. aureus was greater than the SBA of meropenem .
87739
Intervention_Pharmacological
imipenem
87740
Intervention_Pharmacological
meropenem
87741
Intervention_Pharmacological
imipenem plus 1 g of cilastatin
87742
Intervention_Pharmacological
1 g of meropenem
87743
Intervention_Physical
bioassay
87744
Intervention_Physical
high-pressure liquid chromatography
87745
Intervention_Physical
two-compartment model
87746
Intervention_Physical
noncompartmental technique
87747
Outcome_Physical
Serum bactericidal activities
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Outcome_Other
comparative pharmacokinetics
87749
Outcome_Other
pharmacokinetics
87750
Outcome_Physical
serum bactericidal activities ( SBAs )
87751
Outcome_Physical
concentrations of the drugs in serum and urine
87752
Outcome_Other
bioassay and high-pressure liquid chromatography .
87753
Outcome_Physical
mean concentrations of imipenem and meropenem measured in serum
87754
Outcome_Physical
urinary recoveries
87755
Outcome_Physical
areas under the concentration-time curve
87756
Outcome_Physical
SBAs
87757
Outcome_Other
microdilution method of Reller and Stratton
87758
Outcome_Physical
Mean reciprocal bactericidal titers
87759
Outcome_Physical
SBAs
87760
Outcome_Other
half-lives
87761
Outcome_Physical
SBAs against clinically important pathogens
87762
Outcome_Physical
SBA
87763
Outcome_Physical
SBA
87764
Participant_Condition
Twelve healthy male volunteers