Pharmacokinetics of imipenem-cilastatin in neonates

B. J. Freij, G. H. McCracken, K. D. Olsen, N. Threlkeld

Research output: Contribution to journalArticle

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Abstract

Imipenem and its renal dehydropeptidase I inhibitor, cilastatin, were coadministered intravenously in a 1:1 ratio to 30 newborns. Five infants each received single doses of 10, 15, or 20 mg/kg of both drugs. Concentrations in plasma were proportional to the administered dose, and cilastatin achieved consistently higher concentrations than did equivalent doses of imipenem because of its smaller volume of distribution. The pharmacokinetics of both drugs were best described by a one-compartment model. The plasma half-lives of imipenem were 1.7 to 2.4 h, whereas those of cilastatin were 3.9 to 6.3 h. The plasma clearance of cilastatin was approximately one-quarter of that of imipenem in the dose range tested. The urinary concentrations of imipenem were 50% of those of cilastatin despite its higher clearance from plasma. Fifteen additional newborns received five to eight doses of imipenem-cilastatin at 20 mg/kg per dose every 12 h. There was no accumulation of either drug in plasma after repeated administrations, and the mean concentrations in plasma were similar when measured on the first and last days of the multiple-dose study. There was marked intersubject variability, more so for cilastatin. The pharmacokinetics of both drugs in neonates resembled those observed in adults with moderate to severe renal insufficiency. Because the effects of enzyme inhibition on neonates are unknown, additional studies with imipenem-cilastatin (primaxin) are recommended.

Original languageEnglish (US)
Pages (from-to)431-435
Number of pages5
JournalAntimicrobial Agents and Chemotherapy
Volume27
Issue number4
StatePublished - 1985

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Cilastatin
Imipenem
Pharmacokinetics
Newborn Infant
dipeptidase 1
Pharmaceutical Preparations
Renal Insufficiency
imipenem drug combination cilastatin
Kidney
Enzymes

ASJC Scopus subject areas

  • Pharmacology (medical)

Cite this

Freij, B. J., McCracken, G. H., Olsen, K. D., & Threlkeld, N. (1985). Pharmacokinetics of imipenem-cilastatin in neonates. Antimicrobial Agents and Chemotherapy, 27(4), 431-435.

Pharmacokinetics of imipenem-cilastatin in neonates. / Freij, B. J.; McCracken, G. H.; Olsen, K. D.; Threlkeld, N.

In: Antimicrobial Agents and Chemotherapy, Vol. 27, No. 4, 1985, p. 431-435.

Research output: Contribution to journalArticle

Freij, BJ, McCracken, GH, Olsen, KD & Threlkeld, N 1985, 'Pharmacokinetics of imipenem-cilastatin in neonates', Antimicrobial Agents and Chemotherapy, vol. 27, no. 4, pp. 431-435.
Freij, B. J. ; McCracken, G. H. ; Olsen, K. D. ; Threlkeld, N. / Pharmacokinetics of imipenem-cilastatin in neonates. In: Antimicrobial Agents and Chemotherapy. 1985 ; Vol. 27, No. 4. pp. 431-435.
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