Abstract
The effect of probenecid on the disposition of cefpiramide was studied in rats. Cefpiramide (50 mg/kg) was injected into rats through a femoral vein. Probenecid (75 or 150 mg/kg) was administered simultaneously with cefpiramide. The plasma concentration of cefpiramide and the amount excreted into the bile were monitored with a high-performance liquid chromatograph (HPLC). Population pharmacokinetics with Akaike's information criterion (AIC) was applied to analyze the effect of probenecid on the disposition of cefpiramide. The result of the AIC method was compared with that of the χ2 test. It was concluded that probenecid exclusively inhibits the biliary excretion of cefpiramide. The presence of probenecid does not influence the volume of distribution of cefpiramide or the non-biliary elimination rate. The administration of 75 mg/kg of probenecid markedly suppresses the biliary excretion of cefpiramide. However, the effect of 150 mg/kg of probenecid on the elimination rate of cefpiramide is almost the same as that of 75 mg/kg.
