Pharmacokinetics and tolerance after repeated doses of imipenem/cilastatin in patients with severe renal failure

: The pharmacokinetics of imipenem and cilastatin after repeated doses have been studied in six patients with severe renal impairment (mean creatinine clearance 10.4 ml/min/1.73 m2). The patients received nine iv injections of imipenem/cilastatin sodium (500/500 mg) at 12-hour intervals. The imipenem plasma concentration-time profile and the pharmacokinetic parameters on day 5 were similar in all respects to those on day 1. Therapeutic plasma levels of imipenem (greater than or equal to 4 mg/l) were maintained for 8-10 h after administration. Most pharmacokinetic parameters of cilastatin were similar on both days. However, the area under the plasma concentration curve (AUC) was significantly increased on day 5, as a result of some accumulation, but the trough levels stabilized after the third injection. Twice daily administration of imipenem/cilastatin 500/500 mg was felt to be a well tolerated and optimal dose regimen in patients with severe renal failure.