Pharmacokinetic and clinical studies of sy5555 in the pediatric field: Pediatric Study Group of SY5555 (Chief Investigator: Ryochi Fujii)

SY5555, a new oral penem, was pharmacokinetically and clinically evaluated in the pediatric field and the following results were obtained: 1. Pharmacokinetics Pharmacokinetics of SY5555 dry syrup (powder which is dissolved before use) was investigated in 64 children. At a dose level of 3 mg (potency)/kg, Cmax and Tl/2 were 0.33 μg/ml and 0.95 hours (n=1), respectively, in the non-fasting state. At a dose level of 5mg/kg Cmax and Tl/2 were 2.09+1.25μg/m\ and 1.20±1.07 hours, respectively, in the fasting state, and were 1.21 ±0.70μg/ml and 1.33±0.90 hours, respectively, in the non-fasting state. At a dose level of 10 mg/kg, Cmax and T1/2 were 2.96± 1.89μg/ml and 0.89±0.43 hours, respectively, in the fasting state, and were 2.45 ±1.37μg/ml and 1.17±0.53 hours, respectively, in the non-fasting state. At a dose level of 15 mg/kg, Cmax and Tl/2 were 4.30±2.15μg/ml and 0.82±0.09 hours, respectively, in the non-fasting state. Data of Cmax and AUC showed that plasma concentration of the drug depended on dose levels. Urinary recovery rates in the first 6 hours were 1.71% (n=l) in the non-fasting state at a dose level of 3mg/kg, 4.13±1.40% in the fasting state and 4.17±3.29% in the fasting and the non-fasting state, respectively at a dose level of 5 mg/kg, and 6.02% (n=l) and 4.64±2.81%, respectively, at a dose level of 10 mg/kg. At a dose level of 15 mg/kg, urinary recovery rate in the first 6 hours was 7.97% (n = 2) in the non-fasting state. 2. Clinical results 1) Dry syrup the clinical efficacy of the SY5555 dry syrup was evaluated in 506 cases. SY5555 was administered at daily doses of 15~30 mg/kg divided into 3 equal doses to most patients. Daily doses of 12~< 18 mg/kg were given to 46.6% of the patients. the overall clinical efficacy rate was 92.9%, and this drug was effective in 93.0% of the 301 patients for whom the causative pathogens were identified, and in 92.7% of the 205 patients with infections for whom the causative pathogens were unknown. the efficacy rate at daily doses of 12 ~ < 18 mg/kg was 94.5% similar to those obtained at daily doses of 18~ < 27 mg/kg (91.7%) or 27 ~<33mg/kg (91.3%). the bacteriological eradication rate was 82.3%. the efficacy and eradication rates for 62 patients who had not responded to previous chemotherapy of more than three days were 90.3% (56/62) and 72.4%, respectively. Side effects occurred in 36 (6.4%) of 566 patients subjected to safety analyses. the primary side effect was diarrhea but no serious side effects were noted. As abnormal laboratory test results, increases of the eosinophils, elevation of GOT or GPT, and others were observed. These abnormalities are also observed with cephems and to a similar extent. No particular and serious problems were associated with administration of this drug. 2) Tablets Clinical efficacy of SY5555 200 mg (potency) tablets was evaluated in 8 cases, and good to excellent clinical responses were obtained in 7 cases. Bacteriological efficacy was good, and all of the 3 identified causative organisms were eradicated. Neither side effects nor abnormal laboratory test results were observed. 3. Conclusion Based on the above results, SY5555 in dry syrup or tablets is considered to be useful at the standard dose of 5 mg/kg t.i.d. against many infections encountered in the pediatric field. the dosage may be altered according to symptoms (but should not exceed the maximum adult daily dose, 1,200 mg).