Clinical and pharmacokinetic evaluation of imipenem/cilastatin sodium in children

Abstract

Nineteen episodes of infection in 17 children (one had 3 episodes) were treated with imipenem/cilastatin sodium (MK-0787/MK-0791), and the clinical efficacy and side effects were evaluated. The ages of patients ranged from 1 month to 8 years 1 month and their body weights ranged from 3.9 to 25.2 kg. The MK-0787/MK-0791 was administered intravenously by a 30-60 minutes infusion, in doses ranging from 8-42 mg/8-42 mg/kg every 6 to 12 hours for 3 to 40.5 days. Among 18 episodes in 16 patients (one patient proved to have rubella meningoencephalitis and was excluded from evaluation of the clinical efficacy) with bacterial infections including sepsis, pneumonia, acute suppurative thyroiditis and urinary tract infections, the results were excellent in 10, good in 5, fair in 2, and poor in 1 episode. Some side effects were noted; among all 19 episodes in the 17 patients diarrhea was noted in 3, rash in 1, slightly elevated serum transaminases in 1 and thrombocytosis in 1 episode. Pharmacokinetic studies were done in 7 patients whose ages ranged from 3 years 2 months to 13 years 1 month. Plasma concentrations of MK-0787 in 2 children were 19.6 and 20.0 micrograms/ml at 15 minutes and 5.6 and 2.1 micrograms/ml at 2 hours after a 10 mg/10 mg/kg intravenous 30-minute drip infusion of MK-0787/MK-0791. Plasma half-lives of MK-0787 were 1.52 and 0.74 hour, and total urinary recoveries were 54.6 and 71.4% during 0-6 hours. After a 20 mg/20 mg/kg intravenous 30-minute drip infusion into 2 other children, plasma concentrations of MK-0787 were 46.8 and 44.0 micrograms/ml at 15 minutes and 7.8 and 7.4 micrograms/ml at 2 hours. Plasma half-lives were 0.82 and 0.83 hour, and total urinary recoveries were 110.2 and 80.5% during 0-6 hours. Plasma concentrations of MK-0787 were less than 0.2, 0.2 and 1.2 micrograms/ml just before the next doses in 3 patients given 11-20 mg/11-20 mg/kg of MK-0787/MK-0791 every 6-8 hours. The time course of the plasma levels and urinary excretion in these patients were similar to those noted in the previous 4 patients following a single dose. Plasma concentrations of MK-0787 in a girl were 0.3 micrograms/ml just before the next dose and 8.2 micrograms/ml at 2 hours after multiple doses of 14 mg/14 mg/kg every 6 hours for 3 days and then 28 mg/28 mg/kg every 6 hours for 35 days.(ABSTRACT TRUNCATED AT 400 WORDS)