HEPATIC EXTRACTION RATIO OF 5-FLUOROURACIL IN RATS - DOSE DEPENDENCE AND EFFECT OF URACIL AND INTERLEUKIN-2

The hepatic extraction ratios (E(H)) of 5-fluorouracil (FUra) in rats were studied to clarify the disposition of FUra in the liver. The E(H) Of FUra in rats at infusion rates ranging from 0.375 to 3 mg/kg/min d ecreased from 0.750 to 0.225. The E(H) of values of tegafur, a pro-dru g of FUra, were 0.076 to 0.103 over the range of infusion rates, 0.577 to 4.616 mg/kg/min, and were much lower than those of FUra. The E(H) of FUra at an infusion rate of 0.375 mg/kg/min combined with uracil (0 .323 mg/kg/min) was 0.646, which was significantly lower than that of FUra alone, 0.750 (P < 0.001). The E(H) Of FUra combined with interleu kin-2 (IL-2) at an infusion rate of 7500 U/kg/min was significantly hi gher than that of FUra alone (P < 0.01). The dose dependence of the E( H) of FUra and the effects of uracil and IL-2 on the E(H) Of FUra corr esponded with clinical findings. These results suggest that this exper imental model in rats may be useful for predicting the clinical pharma cokinetics and efficacy of FUra. We also studied the effect of IL-2 on the E(H) of mitomycin C (MMC). The E(H) Of MMC combined with IL-2 was higher than that of MMC alone, but the difference was not significant .