Serum bactericidal activities and comparative pharmakokinetics of meropenem and imipenem-cilastatin

• Published in: Antimicrobial agents and chemotherapy 1996, Vol.40 (1), p.105-109
• Main Authors: DREETZ, M, HAMACHER, J, ELLER, J, BORNER, K, KOEPPE, P, SCHABERG, T, LODE, H
• Format: Article
• Language: English
• Subjects: Antibacterial agents; Antibiotics. Antiinfectious agents. Antiparasitic agents; Biological and medical sciences; Medical sciences; Pharmacology. Drug treatments; Proteus mirabilis; Pseudomonas aeruginosa
• ISSN: 0066-4804; 1098-6596
• DOI: 10.1128/aac.40.1.105

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 plus or minus 9.8 and 51.6 plus or minus 6.5 mg/liter, respectively; urinary recoveries were 48.6% plus or minus 8.2% and 60.0% plus or minus 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 plus or minus 14.4 and 70.5 plus or minus 10.3 mg x h/liter, respectively (P less than or equal to 0.02). Imipenem had a mean half-life of 66.7 plus or minus 10.4 min; that of meropenem was 64.4 plus or minus 6.9 min. The volumes of distribution at steady state of imipenem and meropenem were 15.3 plus or minus 3.3 and 18.6 plus or minus 3.0 liters/70 kg, respectively, and the mean renal clearances per 1.73 m super(2) were 85.6 plus or minus 17.6 and 144.6 plus or minus 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 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.