Pharmacokinetic and clinical studies in pediatrics were performed on panipenem/betamipron (PAPM/BP), a combined drug of a carbapenem antibiotic (panipenem) and organic ion inhibitor (betamipron) at a weight ratio of 1: 1.
1. Plasma levels and urinary excretion were studied when PAPM/BP, at 10mg/10mg/kg (4 cases) or 20mg/20mg/kg (5 cases), was administered using intravenous drip infusion in 30 minutes to 9 children (4-14 years old).
The plasma PAPM level at the end of drip infusion was 30.75±4.98μg/ml in the cases administered with 10mg/10mg/kg and 68.72±5.73μg/ml in the cases administered with 20mg/20mg/kg. Drug concentrations then gradually decreased with half-lives of 1.08±0.09 hours and 0.98±0.02 hour, and reached 0.39±0.14μg/ml and 0.62±0.06μg/ml, respectively, after 5.5 hours.
Plasma BP levels at the end of drip infusion was 18.93±3.75μg/ml in the cases administered 10mg/10mg/kg and 37.09±2.68μg/ml in the cases administered 20mg/20mg/kg, and half-lives were 0.55±0.07 hour and 0.61±0.03 hour, respectively; the plasma BP level could not be determined in any cases after 5.5 hours.
Mean urinary recovery rates of PAPM in the first 6 hours after the start of intravenous drip infusion were 33.0±6.1% in the cases administered 10mg/10mg/kg and 21.8±2.3% in the cases administered 20mg/20mg/kg and those of BP were 77.0±2.4% and 76.6±7.3%, respectively.
2. When PAPM/BP, was administrated at 31.3mg/31.3mg/kg thought by intravenous drip infusion in 30 minutes to 1 case of purulent meningitis, PAPM levels were 0.76μg/ml at the end of drip infusion but varied between 0.80 to 1.97μg/ml 30 minutes after the end of drip infusion during 8 days of treatment.
3. PAPM/BP was administered to 43 cases, 47 diseases of bacterial infections in the domain of pediatrics to study its clinical efficacy, bacteriological efficacy and adverse reactions. Single doses were 5.2mg/5.2mg to 31.3mg/31.3mg/kg; frequencies of administration were 3 to 4 times a day, and durations of administration were 3 1/3 to 11 days; and total dosages ranged between 1.125g/1.125g and 11.0g/11.0g.
Responses were rated as “excellent” in acute purulent tonsillitis 6 cases, acute suppurative cholangitis 1 case, acute enteritis 3 cases and purulent meningitis 1 case, as “good” in cellulitis 1 case and acute urinary tract infection 1 case, as “excellent” in 1 and “good” in 3 out of 4 cases of acute purulent otitis media and as “excellent” in 22 and “good” in 7 out of 30 cases of acute pneumonia. In all the evaluable cases, the resluts were rated as “good” or “excellent”.
As for the bacteriological effects on
Staphylococcus aureus 1 strain,
Streptococcus pyogenes 1 strain,
Streptococcus pneumoniae 10 strains,
Haemophilus influenzae 12 strains and
Escherichia coli 1 strain which were detected as the pathogenic bacteria in these cases, the results were rated as “disappeared” in all the cases except 1 strain of
H. influenzae which was rated as “decreased”.
No adverse reactions were observed. As abnormal changes in laboratory data, elevation of GOT was observed in 1 case and increases in platelet counts in 3 cases.
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