Single-dose pharmacokinetics of imipenem-cilastatin in neonates.
The single-dose pharmacokinetics of imipenem (N-formimidoyl thienamycin), a beta-lactam antibiotic, used in combination with cilastatin, a renal dehydropeptidase I inhibitor, were evaluated in 10 neonates 1 to 8 days of age. The imipenem-cilastatin combination was given intravenously over a 15-min period at a dose of 15 or 25 mg/kg. Drug concentrations in serum, urine, and cerebrospinal fluid (when available) were determined by high-pressure liquid chromatography, and plasma disposition of the drugs was described by a two-compartment open model. The mean peak plasma levels of imipenem 30 min postinfusion were 55.4 and 27.2 micrograms/ml, and the mean t1/2 beta values were 2.1 and 1.8 h at doses of 25 and 15 mg/kg, respectively. The calculated volume of distribution was 0.41 liters/kg. In two patients from whom cerebrospinal fluid was obtained 1.5 h postinfusion, imipenem levels were 5.6 and 1.1 micrograms/ml at doses of 25 and 15 mg/kg, respectively, representing 10 and 4% of the 1-h serum levels. No side effects attributable to a single dose of imipenem-cilastatin were noted.
D002851:Chromatography, High Pressure Liquid; D015377:Cilastatin; D003521:Cyclopropanes / Q000008:administration & dosage / Q000009:adverse effects / Q000378:metabolism*; D004150:Dipeptidases / Q000037:antagonists & inhibitors*; D004338:Drug Combinations; D006801:Humans; D015378:Imipenem; D007231:Infant, Newborn; D007700:Kinetics; D013845:Thienamycins / Q000008:administration & dosage / Q000009:adverse effects / Q000378:metabolism*
D003521:Cyclopropanes; D004338:Drug Combinations; D013845:Thienamycins; D015377:Cilastatin; D015378:Imipenem; D004150:Dipeptidases