Pharmacokinetic and clinical studies on panipenem/betamipron in the pediatric field

Abstract

Panipenem/betamipron (PAPM/BP), one of the carbapenems, was studied for its absorption and excretion, and clinical efficacy. The following is a summary of the results: 1. Absorption and excretion: Fourteen patients with their ages between 2 years and 14 years were administered with PAPM/BP 10 mg/kg, 20 mg/kg or 30 mg/kg, in 30-minute intravenous drip infusion. Maximum serum levels of PAPM, at dose levels of 10 mg/10 mg/kg, 20 mg/20 mg/kg and 30 mg/30 mg/kg of PAPM/BP, were 27.37 micrograms/ml, 59.3 micrograms/ml, 91.7 micrograms/ml, respectively, at the end of infusion. The half-lives of the 3 dose levels were all within 0.90-0.96 hour. Mean peak serum levels of BP, at dose levels of 10 mg/10 mg/kg, 20 mg/20 mg/kg and 30 mg/30 mg/kg, were 21.77 micrograms/ml, 35.29 micrograms/ml, 50.08 micrograms/ml, respectively, with half-lives of 0.55-0.63 hour. Urinary recovery rates of PAPM in the first 8 hours after administration at dose levels of 10 mg/10 mg/kg, 20 mg/20 mg/kg and 30 mg/30 mg/kg, were 15.9-31.1%, 15.3-36.9%, 11.0-40.5%, respectively, and those of BP during the same time were 33.1-79.1%, 41.3-93.4%, 12.9-94.4%, respectively. 2. Thirty-nine patients, including 2 with purulent meningitis, 1 with septicemia (suspect), 18 with acute pneumonia, 5 with bronchiolitis, 2 with tonsillitis (unable to receive oral antibiotics), 3 with cervical purulent lymphadenitis, 2 with bacterial enteritis, 6 with urinary tract infections were treated with PAPM/BP at dose levels of 30-100 mg/kg/day. Clinical responses in the patients were excellent or good. Even 2 patients with purulent meningitis were treated with PAPM/BP at dose levels of no less than 20 mg/kg x 3 and 33 mg/kg x 3. Most of respiratory and urinary tract infection cases of moderate severities were treated at dose levels of 30-60 mg/kg/day, i.e., 10 mg/kg x 3 or 20 mg/kg x 3. No adverse reaction was observed. One patient suffered from frequent watery diarrhea but the drug was continued to be administered and the patient recovered quickly. Abnormal laboratory findings were noted, in 2 cases with elevation of platelet, in 1 case with elevation of GOT, in 1 case with elevation of monocyte, in 1 with eosinophilia, in 1 with eosinophilia and decrease in platelet count, in 1 with eosinophilia and elevation of GOT and in 2 with elevation of GOT and GPT, but these abnormalities in the 9 cases were slight and transient.