Multiple-dose pharmacokinetics of imipenem-cilastatin.
We characterized the pharmacokinetic profile of imipenem-cilastatin administered intravenously to six normal volunteers in a dose of 1,000 mg of each drug every 6 h for 40 doses. The plasma concentrations of imipenem and cilastatin 1 h after the end of a 30-min infusion were 18.7 (+/- 2.1) and 19.1 (+/- 4.6), 20.0 (+/- 3.2) and 17.8 (+/- 4.8), and 23.4 (+/- 2.3) and 19.1 (+/- 3.5) micrograms/ml in the 1st, 17th, and 37th dosing intervals, respectively. The central compartment volumes of distribution for imipenem and cilastatin were 0.16 (+/- 0.05) and 0.14 (+/- 0.03) liter/kg, respectively. Elimination half-lives were short: 0.93 (+/- 0.09) h for imipenem and 0.84 (+/- 0.11) h for cilastatin. Plasma clearances were 12.1 (+/- 0.06) liters/h per 1.73 m2 for imipenem and 12.4 (+/- 1.1) liters/h per 1.73 m2 for cilastatin. Renal clearance accounted for 54% of the plasma clearance of imipenem and 69% of the plasma clearance of cilastatin. The concentrations of imipenem in plasma and urine remained above the MICs of the vast majority of pathogens throughout the dosing interval.
D000328:Adult; D000900:Anti-Bacterial Agents / Q000378:metabolism*; D015377:Cilastatin; D003521:Cyclopropanes / Q000378:metabolism* / Q000652:urine; D004334:Drug Administration Schedule; D004338:Drug Combinations; D006207:Half-Life; D006801:Humans; D015378:Imipenem; D007275:Injections, Intravenous; D007700:Kinetics; D008297:Male; D013845:Thienamycins / Q000378:metabolism* / Q000652:urine
D000900:Anti-Bacterial Agents; D003521:Cyclopropanes; D004338:Drug Combinations; D013845:Thienamycins; D015377:Cilastatin; D015378:Imipenem