Single-dose pharmacokinetics of imipenem-cilastatin in neonates

Antimicrob Agents Chemother. 1985 Apr;27(4):511-4. doi: 10.1128/aac.27.4.511.

Abstract

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.

MeSH terms

  • Chromatography, High Pressure Liquid
  • Cilastatin
  • Cyclopropanes / administration & dosage
  • Cyclopropanes / adverse effects
  • Cyclopropanes / metabolism*
  • Dipeptidases / antagonists & inhibitors*
  • Drug Combinations
  • Humans
  • Imipenem
  • Infant, Newborn
  • Kinetics
  • Thienamycins / administration & dosage
  • Thienamycins / adverse effects
  • Thienamycins / metabolism*

Substances

  • Cyclopropanes
  • Drug Combinations
  • Thienamycins
  • Cilastatin
  • Imipenem
  • Dipeptidases