title: Pharmacokinetics and tolerance after repeated doses of imipenem/cilastatin in patients with severe renal failure.
abstract: 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.
authors.forename: L
authors.initials: L
authors.lastname: Verbist
authors.forename: G A
authors.initials: GA
authors.lastname: Verpooten
authors.forename: R A
authors.initials: RA
authors.lastname: Giuliano
authors.forename: M E
authors.initials: ME
authors.lastname: Debroe
authors.forename: A P
authors.initials: AP
authors.lastname: Buntinx
authors.forename: L A
authors.initials: LA
authors.lastname: Entwistle
authors.forename: K H
authors.initials: KH
authors.lastname: Jones
mesh_terms: D000328:Adult; D000368:Aged; D015377:Cilastatin; D003521:Cyclopropanes / Q000009:adverse effects / Q000378:metabolism* / Q000652:urine; D004150:Dipeptidases / Q000037:antagonists & inhibitors*; D005260:Female; D006207:Half-Life; D006801:Humans; D015378:Imipenem; D007676:Kidney Failure, Chronic / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D013845:Thienamycins / Q000009:adverse effects / Q000378:metabolism* / Q000652:urine
chemical_list: D003521:Cyclopropanes; D013845:Thienamycins; D015377:Cilastatin; D015378:Imipenem; D004150:Dipeptidases