Distribution and excretion of methamphetamine and its metabolites in rats. I. Time-course of concentrations in blood and bile after oral administration.

1. Concentration time-courses of methamphetamine and its metabolites in the blood after oral administration of [3H]methamphetamine to rats showed two distinct peaks at 2.5 and 8 h after dosing. The major metabolite present in the blood at all times was unconjugated p-hydroxymethamphetamine. 2. Biliary excretion of radioactivity after oral administration of [3H]methamphetamine to rats was about 30% dose in 24h. The major metabolite in the bile was p-hydroxymethamphetamine glucuronide. 3. Blood and bile were collected simultaneously from a rat fitted with a T-tube cannula in the common bile duct, and time-courses of blood and bile concn. of the drug and metabolites were investigated. The observation of two peaks in both blood and bile indicates enterohepatic circulation of the drug and metabolites.