Overall Clinical Evaluation of Panipenem/Betamipron Against Infections in Pediatric Field

To conduct a basic-clinical study on newly developed panipenem/betamipron (CS-533/CS-443, PAPM/BP) against various infections in pediatrics,a study group was organized and a joint research by 17 institutions and their related hospitals was undertaken. The obtained results are as follows. 1. Blood concentrations and urinary excretion Pharmacokinetics of PAPM/BP in children was studied using 30 minutes intravenous drip infusion of 10 mg/10 mg/kg, 20mg/20mg/kg and 30 mg/30 mg/kg, respectively. Maximum blood levels of PAPM/BP were observed at the completion of drip infusion and were 26.72- 8.78 μg/ml/ 18.33-8.54 μg/ml (mean-S.D.) with administration of 10mg/10mg, 64.80-18.50 μg/ml/38.74- 16.41μg/ml with administration of 20mg/20mg and 91.70-29.42 μg/ml/50.08-22.41 μg/ml with administration of 30 mg/30 mg. Dose dependency was noted with these doses. The half-life was about 1 hour for PAPM and about 0.5 hour for BP. As for urinary excretion, PAPM was excreted about 30% and BP about 70% in the first 6 hours after the start of drip infusion. 2. Clinical results Twenty-five cases of exclusion and drop-out were deducted from a total of 391 cases and 8 cases having 2 diseases concurrently were added to the remaining 366 cases, hence 374 cases were evaluated in the study as the subjects of analysis of clinical effects. As for clinical effects in cases where pathogenic bacteria were detected, 215 out of 221 cases were rated as effective or above, hence the efficacy rate of 97.3% was obtained. In cases where pathogenic bacteria were not detected, 145 out of 153 cases were rated as effective or above, thus the efficacy rate was 94.8% which is similar to that in the cases where pathogenic bacteria were detected. The daily dose levels most commonly employed were 30 to 60 mg/kg (as PAPM) administered in 3 divided doses a day, and this regimen method accounted for 52.7% of the total cases, and the efficacy rate with this regimen was 97.0%. As for the bacteriological effect 87 (96.7%) out of 90 strains of Gram-positive bacteria (GPB) disappeared and 136 (91.3%) out of 149 strains of Gram-negative bacteria (GNB) disappeared upon the treatment. The overall bacterial eradication rate for the pathogenic bacteria was 93.4%. The efficacy rate of this drug preparation in cases in which other antibacterial drugs administered for more than 3 days proved to be ineffective was 95.9% (71/74). The bacterial eradication rate for Gram-positive bacteria was 100% (17/17) and that for GNB was 86.2% (25/29). 3. Side effects and abnormal laboratory data A study on the safety was conducted in 380 cases excluding 11 cases. Side effects were noted in 9 cases (2.4%), consisting of skin rash in 3, urticaria in 1, soft stool in 2 and diarrhea in 3. Abnormal laboratory data were found in 64 cases, consisting mainly of elevations in platelet count, increases in eosinophils and elevations of trans-aminase. Side effects and abnormalities in laboratory data were not particularly serious and disappeared or returned to normal with discontinuation or completion of the medication with this preparation.