Metabolism of papaverine. II. Species differences

1. The urinary and biliary excretion of radioactive products in a 6 hr period after intravenous administration of [3H]papaverine was studied in rat, guinea-pig, rabbit, cat and dog. All species excreted metabolites extensively in the bile; only in rabbit and guinea-pig is urinary excretion important. 2. Metabolites in urine and bile of all species studied are mainly monophenolic compounds conjugated to glucuronic or sulphuric acid. Differences in the excretion patterns of the metabolites between different species are only quantitative. 3. Blood or plasma levels of papaverine after intravenous injection decreased with half-lives of approximately 12, 15, 22, 60 and 60 min for rabbit, rat, guinea-pig, cat and dog, respectively. The metabolites disappeared much more slowly than papaverine from the plasma. 4. Binding of papaverine to plasma proteins, as studied by equilibrium dialysis, was more than 90% in all species.