We investigated pharmacokinetics and clinical effectiveness of a newly developed cephem antibiotic cefozopran (SCE-2787, CZOP) against various pediatric infections in 18 institutions and their affiliates. We obtained the following results. 1. Serum concentration and urinary excretion rates Pharmacokinetics of CZOP in children was examined after intravenous injection and 30-minute drip infusion of 10, 20 and 40mg/kg of CZOP. Peak serum concentrations of CZOP in 30 minutes after intravenous injection were 21.7, 51.5 and 77.8μg/ml, respectively, showing a clear dose response. Half-lives were 1.99, 1.85 and 1.67 hours, respectively. In the first 6 hours after administration, urinary excretion rates of CZOP were 87.3, 67.4 and 84.1%, respectively. In the cases of 10, 20 and 40mg/kg administration of CZOP 30-minute drip infusion, peak serum concentration of CZOP in 30 minutes, when the infusion was completed, were 38.1, 72.8 and 95.6 μg/ml, respectively. Again, there was a clear dose response. Half-lives were 1.67, 1.69 and 1.43 hours, respectively. In the first 6 hours after administration, urinary excretion rates of CZOP were 53.9, 59.7 and 77.3%, respectively Cerebrospinal fluid concentrations of CZOP administered by intravenous injection of 50 mg/kg to patients with purulent meningitis were 1.6 to 43.4μg/ml in 1 to 1.5 hours after administration. 2. Clinical study Clinical efficacy was evaluated in 337 cases. The largest number of cases, 138 cases, were found in 2 to < 6-year olds. The majority of the patients were under age 9, and 70 cases were of less than 1-year old infants. 183 cases were males and 154 cases were females. In terms of illness, a majority, or 185 cases, suffered from pneumonia, followed by 39 cases of UTI and 23 infections of the skin and soft tissue. There were 7 cases of purulent meningitis. In 218 cases, CZOP was administered at a daily dose of 60~< 80 mg/kg. The drug was administered for 6~10 days, the most frequent duration, in 188 cases. In the cases where causative organisms were identified (group A), the efficacy rates ("excellent" and "good") obtained were 100% (5/5) against purulent meningitis, 100% (2/2) against sepsis, 98.3% (119/121) against pneumonia, 100% (13/13) against acute bronchitis, 100% (11/11) against upper respiratory tract infection, 96.3% (26/27) against UTI. Overall, "excellent" and "good" responses were observed in 97.5% (197/202) of cases with known causative organisms. In the cases in whom causative organisms were not identified (group B), the efficacy rates were 98.4% (63/64) against pneumonia, 100% (9/9) against acute bronchitis, 50% (3/6) against upper respiratory tract infection, 100% (12/12) against UTI, 92.9% (13/14) against purulent lymphadenitis, 100% (17/17) against skin and soft tissue infection, 100% (2/2) against purulent meningitis and 50% (1/2) against suspected sepsis. The overall efficacy rate was 95.6% (129/135) for all the cases where causative organisms were not identified. Especially, the efficacy rates for "excellent" were very high, and they were 74.3% (150/202) for group A, 55.6% (75/135) for group B. The efficacy rate was 97.0% (258/266) for the group given a daily dose of 40~80 mg/kg (t.i.d.). Bacteriologically, 77 Gram-positive strains (96.3%) out of 80 strains as well as 155 Gram-negative strains (94.5%) out of 164 strains were eradicated. Thus out of the 244 strains of known causative bacteria, 232 strains (95.2%) were eradicated. In 93 cases where more than 3 days of previous treatment resulted in "poor" efficacy, CZOP showed "excellent" or "good" responses in 90 cases (96.8%). Bacteriologically, 24 Gram-positive strains (96.0%) were eradicated out of the 25 strains on which previous treatment was not effective. Moreover, out of the 57 Gram-negative strains, 53 strains (93.0%) were eradicated. Altogether, 77 strains (93.9%) out of 82 were eradicated following treatment with CZOP. 3. Side effects and abnormal laboratory test results The safety was evaluated in 364 cases. 11 cases (3.0%) showed side effects including 7 cases (1.9%) of diarrhea (loose stools and watery stools) and 4 cases (1.1%) of rash (exanthema and wheal). Abnormal laboratory test results were observed in 54 cases, which were mostly increases in eosinophil counts (in 20 cases, or 6.3%) and GPT (also in 20 cases, 6.3%). None of the side effects or abnormal laboratory test results were serious. They disappeared or lessened during continued administration or by discontinuation of treatment. In the pediatric cases involving infants less than 1 year old, none of side effects and laboratory test abnormalities were found to be serious. These results indicated that CZOP is highly safe. Based on these results, it has been assured that CZOP has an optimum characteristic as a parenteral cephem and is a highly useful drug for treating various pediatric infections.
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