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.