FUNDAMENTAL STUDIES ON EXCRETION OF PIVMECILLINAM IN BILE

Abstract

Excretion of pivmecillinam (PMPC) in bile was investigated using normal and hepatic disoder (intramuscular injection of carbon tetrachloride, 0.5g/kg twice) rabbits. Bile and blood were collected hourly (0.5-8 hours) and both concentrations and rates between both (passage), and excretion rates were investigated. Ampicillin (AMPC) was chosen as a control drug.
1. When PMPC was given orally to the normal rabbit in a dose of 200mg/kg, a bile concentration after 0.5hour was 138.08μg/ml and a peak value was attained. The rate to plasma concentration was 22.67. An excretion rate was 0.224%.
2. When PMPC was given orally to the hepatic disorder rabbit in a dose of 200mg/kg, a bile concentration after 0.5hour was 26.67μg/ml. A peak value of 28.87μg/ml was attained after 4 hours. Their rates to plasma concentrations were 13.27 and 8.02, respectively. An excretion rate was 0.058%. Bile and plasma concentrations, rates of bile to plasma and excretion rates of the hepatic disorder groupwere lower than those of the normal group. Disturbancesof hepatic functions were checked by biochemical tests, i.e. GOT, and so on.
3. When ABPC as a control drug was given orally to the rabbit in a dose of 200mg/kg, plasma concentrations of hepatic disorder group were higher than those of the normal group, but rates of bile to plasma concentrations and excretion rates of the hepatic disorder group were lower than those of the normal group.
4. Bile concentrations and excretion of PMPC were significantly higher than those of ABPC in the normal group. In the hepatic disorder group, however, no statistical difference was observed between them.