[Pharmacokinetic and clinical evaluations of imipenem/cilastatin sodium in neonates and premature infants].
Pharmacokinetic and clinical studies on imipenem/cilastatin sodium (IPM/CS), a beta-lactam antibiotic of the carbapenem class and its renal dehydropeptidase-I inhibitor in a 1:1 ratio, were performed in neonates, premature infants and an infant. IPM/CS was administered intravenously to 4 neonates and 5 premature infants at a dose level of 10 mg/kg. Plasma levels and urinary excretion of IPM and CS were determined in 2 neonates and 2 premature infants after 30-minute infusion, and in 2 neonates and 3 premature infants after 1-hour infusion. Plasma and cerebrospinal fluid (CSF) concentrations of IPM and CS were determined in 2 cases with purulent meningitis with ages of 2 and 26 days and 1 with purulent meningitis/bacteremia with an age of 4 days. The drug was administered to a total of 31 patients with ages between 0 and 30 days, consisting of neonates, premature infants and an infant (24 suffering with various bacterial infections, 5 treated for prophylaxis of infections and 2 treated for aseptic meningitis diagnosed at the completion of therapy) by intravenous drip infusion in a mean daily dose level of 50.1 mg/kg in 2 to 4 divided doses for 9 days on the average. Clinical efficacy, prophylactic effectiveness and bacteriological response of IPM/CS were evaluated in 29 cases. Adverse effects and abnormal laboratory test results were examined in 31 cases including 2 drop-out cases. The results obtained are summarized as follows. 1. Plasma concentrations of IPM and CS after 30-minute infusion of the drug reached their peaks at the end of administration, and obtained values were 22.4 to 29.0 micrograms/ml for IPM and 26.3 to 34.6 micrograms/ml for CS, thus peak plasma levels of CS were a little higher than IPM. Plasma half-lives of IPM were 1.05 to 2.43 hours, and those of CS were 1.24 to 4.76 hours, and the half-life of CS tended to be longer than that of IPM. Drug concentrations in plasma after 1-hour infusion of IPM/CS reached their peaks at the end of administration and the levels of CS (25.7 to 32.0 micrograms/ml) were a little higher than those of IPM (20.8 to 23.9 micrograms/ml). Plasma half-lives of IPM were 1.40 to 1.63 hours, whereas those of CS were 1.51 to 2.90 hours. The half-life of CS tended to be longer than IPM. 2.(ABSTRACT TRUNCATED AT 400 WORDS)
Motohiro
T
T
Department of Pediatrics, School of Medicine, Kurume University.
Sakata
Y
Y
Oda
K
K
Kawakami
A
A
Tanaka
K
K
Koga
T
T
Shimada
Y
Y
Tomita
S
S
Fujimoto
T
T
Tominaga
K
K
D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001424:Bacterial Infections / Q000188:drug therapy* / Q000378:metabolism; D015377:Cilastatin / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000077728:Cilastatin, Imipenem Drug Combination; D002986:Clinical Trials as Topic; D004338:Drug Combinations / Q000493:pharmacokinetics / Q000627:therapeutic use; D005260:Female; D006801:Humans; D015378:Imipenem / Q000493:pharmacokinetics / Q000627:therapeutic use*; D007231:Infant, Newborn; D007235:Infant, Premature, Diseases / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D015337:Multicenter Studies as Topic
D000900:Anti-Bacterial Agents; D004338:Drug Combinations; D015377:Cilastatin; D015378:Imipenem; D000077728:Cilastatin, Imipenem Drug Combination