Studies on the Metabolic Fate of Lamivudine (I): Absorption, Metabolism and Excretion of Lamivudine in Rats.

Abstract

The absorption, metabolism and excretion of nucleoside analogue, lamivudine, were investigated after a single oral administration of 3H-lamivudine to rats at a dose of 2 mg/kg. 1. The total radioactivity in plasma reached the maximum at about 1 hour after oral administration, and declined rapidly with a half-life of about 2 hours. The absorption of 3H-lamivudine after oral administration was slightly decreased by feeding. 3H-lamivudine was well absorbed in each site of small intestine but not stomach. 2. The concentrations of unchanged drug in plasma reached the maximum within 1 hour after oral administration of lamivudine at 2 mg/kg, and declined rapidly with a half-life of about 1 hour. The bioavailability accounted for 81.9% and 76.7% in male and female rats, respectively. Significant linearity of AUC was observed at the dose range of 2 to 10 mg/kg in male rats. 3. The excreted radioactivity in male and female rats was 69.3% and 74.1% of the dose in urine and 29.1% and 23.7% in feces, respectively, up to 168 hours after oral administration. The majority of the dosed radioactivity was excreted into urine within 24 hours post dose. Less than 1 % of the dose was recovered in the bile within 48 hours post dose. 4. Radio-HPLC analysis of the collected urine indicated that virtually all of the radioactivity in the urine consisted of the unchanged lamivudine.