Pharmacokinetic and clinical studies on cefodizime in the pediatric field. Pediatric Study Group of Cefodizime

Abstract A multi-center open study was conducted to investigate cefodizime (CDZM), a newly developed cephem antibiotic, from pharmacokinetic, bacteriological and clinical aspects, in the pediatric field with the participation of 17 institutions and their related facilities. The results are summarized as follows: 1. Serum concentrations and urinary excretion: The pharmacokinetics in pediatric patients was investigated with a dose of 20 mg/kg, via a bolus intravenous injection or intravenous drip infusion over 30 or 60 minutes. The results were nearly the same as those in adult patients. Mean serum concentrations 5 minutes after a bolus intravenous injections were: 105.5, 264.0 and 461.7 micrograms/ml with 10, 20 and 40 mg/kg, respectively, and T 1/2 (beta)'s for the 3 dosages were 1.75, 1.92 and 1.88 hours, respectively. With 30-minute intravenous drip infusion, mean serum concentrations at the end of infusion were: 90.5 micrograms/ml with a dose level of 10 mg/kg, 178.3 micrograms/ml with 20 mg/kg, and 322.8 micrograms/ml with 40 mg/kg, and T 1/2 (beta)'s for these dosages were 1.90, 2.15 and 1.93 hours, respectively. With 60-minute intravenous drip infusion, mean serum concentrations at the end of infusion were: 66.3 micrograms/ml with a dose level of 10 mg/kg, 136.0 micrograms/ml with 20 mg/kg and 259.2 micrograms/ml with 40 mg/kg, and T 1/2 (beta)'s for these dosages were 1.43, 2.05 and 1.46 hours, respectively. In 8 hours after administration of CDZM, urinary excretion rates were 82.1, 77.7 and 76.5% for bolus intravenous injections of 10 mg/kg, 20 mg/kg and 40 mg/kg, respectively, and 83.3, 71.3 and 68.1% for 30-minute intravenous drip infusions of 10 mg/kg, 20 mg/kg and 40 mg/kg, and 84.4 and 84.3% for 60-minute intravenous drip infusions of 20 mg/kg and 40 mg/kg, respectively. 2. Concentrations in cerebrospinal fluid: Penetrations into cerebrospinal fluid in patients with purulent meningitis reached levels of 1.96-9.48 micrograms/ml with administration of CDZM at 50 mg/kg in acute cases within 6 days after onset. The penetration rates of CDZM were about a median range among injectable beta-lactam agents. 3. Of 457 cases treated with CDZM, 53 cases were excluded from the clinical evaluation. Clinical efficacies were evaluated as "excellent" in 126 and "good" in 78 out of 221 case from which causative agents were isolated, with an efficacy rate of 92.3%. Efficacies were "excellent" in 97 and "good" in 69 out of 183 cases from which pathogens were not isolated giving an efficacy rate of 90.7%.(ABSTRACT TRUNCATED AT 400 WORDS)