[Experimental and clinical studies on BRL 25000 (clavulanic acid-amoxicillin) granules in the pediatric field].

BRL 25000 granules (containing 2 parts amoxicillin and 1 part clavulanic acid) have been studied fundamentally and clinically. The MICs of BRL 25000 against strains of S. aureus, E. coli, K. pneumoniae which were resistant to CEZ and beta-lactamase producing strains of H. influenzae were determined. The MICs of BRL 25000 at an inoculum of 10(6) cells/ml were 1/4 to 1/128 of those of AMPC and, in particular, the MICs of BRL 25000 were especially reduced against the organisms for which those of AMPC were more than 100 micrograms/ml. The pharmacokinetics of BRL 25000 were studied in 46 children at dose levels of 7.5 mg (8 fasting children, 7 non-fasting children), 10 mg/kg (4 fasting, 4 non-fasting), 15 mg/kg (4 fasting, 4 non-fasting), 20 mg/kg (8 fasting, 7 non-fasting). The peak serum concentrations in fasting children were marginally higher than those in non-fasting subjects. Values for AMPC and CVA from BRL 25000, dosed at 7.5, 10, 15 and 20 mg/kg to fasting children, 0.5-1 hour after dosing were 4.86 and 2.36 micrograms/ml, 5.20 and 1.69 micrograms/ml, 7.50 and 3.27 micrograms/ml, 9.38 and 6.30 micrograms/ml, respectively. In non-fasting subjects, corresponding values were 2.84 and 1.01 micrograms/ml, 4.53 and 2.10 micrograms/ml, 7.29 and 4.08 micrograms/ml, 6.83 and 2.96 micrograms/ml, respectively. The biological half-lives of AMPC and CVA, following the administration of BRL 25000, show no significant difference between the fasting and non-fasting states. Values for AMPC and CVA in fasting children were 0.85-1.15 hours and 0.64-1.03 hours, and in non-fasting children, 1.18-1.79 hours and 0.78-1.02 hours, respectively. The time to reach the peak serum concentration and half-lives were similar for AMPC and CVA when dosed as BRL 25000. Peak urinary concentrations for BRL 25000 (AMPC and CVA) at dose levels of 7.5, 10, 15, 20 mg/kg to fasting children were 681.8 and 148.2 micrograms/ml, 247.1 and 66.3 micrograms/ml, 484.2 and 149.1 micrograms/ml, 1,796.5 and 372.0 micrograms/ml, whilst in the non-fasting state the values were 496.3 and 83.2 micrograms/ml, 991.1 and 156.7 micrograms/ml, 2,397.5 and 460.7 micrograms/ml, 1, 896.3 and 323.4 micrograms/ml, respectively. The peak urinary concentration in the fasting state was observed at 0-2 hours after dosing, and in non-fasting individuals it occurred at 2-4 hours after dosing.(ABSTRACT TRUNCATED AT 400 WORDS)