Metabolism of papaverine. III. Effect of phenobarbital, 3-methylcholanthrene and SKF 525-A pre-treated in vivo and in vitro.

1. The metabolism of papaverine was studied in vitro using the 9000 g fraction of rat liver. Apparent Km and Vmax values were 1.6 X 10-5 M and 34 nmol/g/min. Three monodemethylated metabolites were found by t.l.c. 2. Pre-treatment of rats with phenobarbital enhanced the activity of papaverine O-demethylase, whereas pre-treatment with 3-methylcholanthrene did not. Pre-treatment with SKF 525-A, or addition of AKF 525-A invitro markedly inhibited the enzyme. 3. Pre-treatment of the rats with phenobarbital enhanced the biliary elimination rate of papaverine metabolites, whereas SKF 525-A pre-treatment slowed this elimination.