title: Single-dose pharmacokinetics of imipenem-cilastatin in pediatric patients.
abstract: The single-dose pharmacokinetics of two dosages of imipenem-cilastatin (1:1), 10 and 25 mg/kg, were studied in ten children. Plasma concentrations, half-lives, and areas under the curve of both imipenem and cilastatin was significantly greater at the 25 mg/kg dosage but the half-lives and clearances of the two drugs were similar to each other only at the larger dose. After a 25 mg/kg dose, the mean peak and trough (6 hr) plasma concentrations of imipenem were 78.8 and 0.68 micrograms/ml, respectively, and the half-lives of imipenem and cilastatin were 1.12 and 0.97 hr, respectively. Urinary excretion of imipenem was 43-47% during the 6 hr following administration of either dosage. No clinical or laboratory toxicity was noted. A 25 mg/kg dose of imipenem-cilastatin maintains serum concentrations of imipenem above the minimum inhibitory concentration (MIC) of potential pathogens for 4-6 hr and seems appropriate for multiple-dose studies. Our data suggest that a minimum dosage, greater than 10 mg/kg, of cilastatin may be required to prolong the half-life of imipenem to adult values.
authors.forename: D
authors.initials: D
authors.lastname: Engelhard
authors.forename: I
authors.initials: I
authors.lastname: Shalit
authors.forename: H R
authors.initials: HR
authors.lastname: Stutman
authors.forename: R
authors.initials: R
authors.lastname: Greenwood
authors.forename: J
authors.initials: J
authors.lastname: Griffis
authors.forename: M I
authors.initials: MI
authors.lastname: Marks
mesh_terms: D002648:Child; D002675:Child, Preschool; D015377:Cilastatin; D003521:Cyclopropanes / Q000008:administration & dosage / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D006801:Humans; D015378:Imipenem; D007700:Kinetics; D008657:Metabolic Clearance Rate; D013845:Thienamycins / Q000008:administration & dosage / Q000378:metabolism*
chemical_list: D003521:Cyclopropanes; D004338:Drug Combinations; D013845:Thienamycins; D015377:Cilastatin; D015378:Imipenem