Disposition of gemcitabine in rat and dog after single and multiple dosings

1. The disposition of radioactivity has been studied in rat and dog after intravenous administration of a single 10 mg/kg dose or multiple 1 mg/kg/day doses of 14C-gemcitabine. 2. Radioactivity was eliminated from the blood in a biphasic manner with half-lives of approximately 2 and 15 h in both the male and female rat. The concentration of radioactivity in the blood 24 h after the fifth dose was 4.4 times higher than that found after the first dose. In the male dog, the concentration of radioactivity in the blood showed a plateau during the first 2 h post-dose administration. 3. Radioactivity was rapidly and widely distributed throughout the body in both the male and female rat at 5 min after administration. Radioactivity was rapidly eliminated from the tissues with no evidence of accumulation. 4. After 120h, male rat excreted 95.2 and 1.9% of the dose in the urine and faeces respectively. Similar excretion patterns were observed in female rat and male dog. In rat, excretion of radioactivity in the urine 24 h after daily dosing was nearly constant, but excretion of radioactivity in the faeces slightly increased with increasing number of doses.