[Pharmacokinetic and clinical studies of cefditoren pivoxil in the pediatric field. Pediatric Study Group of ME1207].

Cefditoren pivoxil (ME1207) in granules, a new oral cephalosporin, was pharmacokinetically and clinically evaluated in the pediatric field and the following results were obtained: 1. Pharmacokinetics In infants administered single oral doses of 3 mg (potency)/kg and 6 mg/kg, the Cmax was 1.54 +/- 0.68 and 2.85 +/- 1.03 micrograms/ml; Tmax, 2.27 +/- 1.08 and 2.06 +/- 1.16 hours; T 1/2, 2.22 +/- 1.95 and 1.68 +/- 0.66 hours; and AUC (0-infinity), 7.43 +/- 3.68 and 11.90 +/- 4.51 micrograms.hr/ml, respectively. These values have indicated that the drug has a dose-dependent pharmacokinetic behavior. Urinary concentrations peaked in 2-4 hours after administration. Urinary recovery rates in the first 8 hours were 19.4 +/- 6.6% at 3 mg/kg and 17.1 +/- 5.2% at 6 mg/kg. 2. Clinical results The clinical efficacy of the drug was evaluated in 445 patients with various infections. Cefditoren pivoxil was administered at daily doses of 9-18 mg/kg divided into 3 equal doses to most patients. Daily doses of > 7.5-10.5 mg/kg were given to 48.8% of the patients. The overall clinical efficacy rate was 97.3%, and this drug was effective in 97.5% of the 319 patients for whom the causative pathogens were identified and in 96.8% of the 126 patients with infections for whom the causative pathogens were unknown. The efficacy rate at daily doses of > 7.5-10.5 mg/kg was 97.2%, similar to that obtained at daily doses of > 10.5-19.5 mg/kg (97.0%). The bacteriological eradication rate was 90.4%. The efficacy and eradication rates for 66 patients who had not responded to previous chemotherapy were 95.5% (63/66) and 89.4%, respectively. Side effects occurred in 19 (4.2%) of 456 patients subjected to safety analyses. The primary side effect was diarrhea but no serious side effects were noted. As abnormal laboratory test results, moderate increases of the eosinophils and platelets counts as well as moderate elevations of the transaminases were observed. These abnormalities are also seen with other cephems and to a similar extent. No particular and serious problems were associated with administration of this drug. Based on the above results, cefditoren pivoxil is considered to be very useful at a dose level of 3 mg/kg t.i.d. against most infections encountered in the pediatric field.