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Abstract
1. The metabolism of 14C-gemcitabine in the male rat has been studied after intravenous administration of a single dose (10 mg/kg) or five doses (1 mg/kg/day) of 14C-gemcitabine. The metabolism in male dog has been studied after only single dosing. The effects of gemcitabine on hepatic drug-metabolizing enzymes in rat has also been studied. 2. The concentration of gemcitabine in the plasma was 11.84 micrograms/ml at 5 min, and then rapidly decreased after a single administration to rat. A deaminated uracil analogue of gemcitabine progressively increased with time. Gemcitabine and the uracil metabolite accounted for 80.0 and 11.8% of the radioactive dose in the 0-24-h urine samples respectively. Gemcitabine was the major component identified in lung, liver and kidney at 5 min after administration. 3. After repeated administration to rat, metabolites in the plasma and tissues were not remarkably different from those found after a single administration. 4. After a single administration to dog, the plasma concentration of gemcitabine was 12.39 micrograms/ml at 5 min. Gemcitabine and the uracil metabolite accounted for 8.3 and 71.8% of the dose in the 0-24-h urine samples respectively. 5. No differences were observed in enzymatic activities per whole liver between the gemcitabine-treated and control rat.
Published Version
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