[Pharmacokinetic and clinical studies of S-1108 in the pediatric field. Pediatric Study Group of S-1108].

Abstract

S-1108 in granules, a new oral cephem antibiotic, was pharmacokinetically and clinically evaluated in the pediatric field and the following results were obtained. 1. Pharmacokinetics S-1108 was administered at single doses of 2, 3, 4, 6 mg/kg orally and the following results were obtained on Cmax, T 1/2 and AUC, respectively: Cmax: 0.79, 1.03, 1.39, 1.06 micrograms/ml, T 1/2: 1.28 +/- 0.40, 1.27 +/- 0.65, 1.10 +/- 0.29, 1.83 hrs., AUC: 2.65 +/- 0.63, 3.99 +/- 2.77, 5.25 +/- 1.83, 5.15 micrograms.hr/ml. These values indicated a dose-dependent pharmacokinetic behavior. Urinary recovery rates were 12.5-30.0% in the first 8(6) hours after administration. 2. Clinical results The clinical efficacy of S-1108 was evaluated in 456 patients with various infections. S-1108 was administered at a dose of 2-4 mg/kg three time a day to most patients. The overall clinical efficacy rate was 95.0%. In 294 cases with identified causative pathogen, the clinical efficacy rate was 96.9%, and the bacteriological eradication rate was 89.0%. Side effects occurred in 18 (3.23%) of 558 patients subjected to safety analyses. The main side effect was diarrhea but those side effects were mild and reversible. Abnormal laboratory test results were observed in 25 cases, (eosinophilia and elevated GOT and GPT). These abnormalities were not dose-dependent and also seen with other cephems to a similar extent. No particular and serious problems were associated with administration of this drug. Based on the above results, S-1108 is considered to be very useful at a standard dose of 2-4 mg/kg t.i.d. against most infections encountered in the pediatric field out-patient clinic.