Apomorphine: bioavailability and effect on stereotyped cage climbing in mice

Plasma levels fo apomorphine and its conjugates were studied following intravenous, intraperitoneal, and oral administrations to mice. Following hydrolysis, apomorphine and its conjugates were assayed by high-performance liquid chromatography. The absolute bioavailability of apomorphine was 4%. A significant first-pass effect due to extensive conjugation in the liver was postulated based on calculated bioavailabilities and comparison of plasma levels of apomorphine and its conjugates following oral, intraperitoneal, and intravenous administrations. Apomorphine-induced stereotypical cage climbing in mice was investigated following administration of apomorphine by the three routes. Analysis of time-course data obtained from the cage-climbing experiments indicated an absolute bioavailability of 16% for apomorphine.