Effects of phenobarbital on digitoxin metabolism in guinea-pig liver slices

Abstract

1. [³H]Digitoxin was incubated for 2–5 h with liver slices from control and phenobarbital-pretreated guinea-pigs. Metabolites were the same in both groups.

2. After 5 h incubation, a 6-fold increase in unmetabolized digitoxin was found in the phenobarbital-pretreated group compared with controls.

3. The major metabolite extracted by chloroform is formed by hydroxylation at an unknown position of the cardenolide nucleus, which is not the 12β-hydroxy position. Only half the amount of this metabolite was formed in livers of pretreated animals, compared to controls, in 2 h, after 5 h incubation similar amounts occurred in both groups.

4. Water-soluble metabolites decreased 2-fold in phenobarbital-pretreated animals at 2 and 5 h of incubation.