Metabolism of gemcitabine in rat and dog

Abstract

1. The metabolism of ¹⁴C-gemcitabine in the male rat has been studied after intravenous administration of a single dose (10mg/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 μ/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 μ/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.