Clinical pharmacology of imipenem and cilastatin in premature infants during the first week of life.
The first-dose and multidose pharmacokinetics of imipenem and cilastatin were evaluated in 41 premature infants during their first week of life. Premature infants (gestational age, less than or equal to 37 weeks) were assigned to receive 10-, 15-, 20-, or 25-mg/kg doses of imipenem-cilastatin (1:1) as a single- or multiple-dose regimen. A total of 39 infants received a single dose, whereas 18 infants received multiple doses. No differences were observed in pharmacokinetic parameter estimates for either agent relative to the dose administered or infant body weight; thus, the data were pooled. Elimination half-life, steady-state volume of distribution, and body clearance averaged 2.5 h, 0.5 liter/kg, and 2.5 ml/min per kg, respectively, for imipenem and 9.1 h, 0.4 liter/kg, and 0.5 ml/min per kg, respectively, for cilastatin. Similar values for these parameter estimates were observed after multidose administration, although substantial accumulation of cilastatin in serum was observed. A total of 21% of the imipenem and 43% of the cilastatin were excreted unchanged in the urine over a 12-h collection period. Corresponding renal clearances averaged 0.4 and 0.2 ml/min per kg for imipenem and cilastatin, respectively. Substantial differences were observed in the route by which imipenem was cleared from the body compared with data from adult volunteers. These data suggest that infants should receive an imipenem dose of 20 mg/kg administered every 12 h for the treatment of bacterial infections outside the central nervous system.
Reed
M D
MD
Division of Pediatric Pharmacology, Rainbow Babies and Childrens Hospital, Cleveland, Ohio.
Kliegman
R M
RM
Yamashita
T S
TS
Myers
C M
CM
Blumer
J L
JL
D015377:Cilastatin / Q000493:pharmacokinetics*; D006801:Humans; D015378:Imipenem / Q000493:pharmacokinetics*; D007231:Infant, Newborn; D007234:Infant, Premature / Q000378:metabolism*
D015377:Cilastatin; D015378:Imipenem