[Dose, administration time and route and hepatic function-dependent metabolism of 5-FU in mice].
Pharmacokinetic studies of 5-FU in normal and Sarcoma 180-bearing mice were performed, and the following results obtained: When the administered dose of 5-FU was increased, it was found that there was an increase in the half-life and AUC (area under the concentration curve) and a lower rate of plasma clearance. When the drug was administered at equal doses of 40 mg/kg, the rate of clearance was high in the order of p.o. greater than continuous infusion greater than i.v. bolus. When Sarcoma 180-bearing mice were injected with CCl4 to induce liver dysfunction and subsequently administered 5-FU, the AUCs of 5-FU in the plasma and tumor tissue were increased by 2 and 1.3 times, respectively, as compared with non-treated mice. The Vmax (nmol/mg protein/min) of DHU (dihydrouracil dehydrogenase) in the liver homogenate from normal mice was 1.18 and found to be 0.70 in CCl4-treated mice. In conclusion, the pharmacokinetics of 5-FU were found to be dependent on the dose, infusion time, administration route and liver function, which seem to be correlated with the capacity of the catabolic enzyme, DHU.
D000284:Administration, Oral; D000818:Animals; D050744:Dihydrouracil Dehydrogenase (NAD+); D004305:Dose-Response Relationship, Drug; D005472:Fluorouracil / Q000008:administration & dosage / Q000378:metabolism*; D007700:Kinetics; D008099:Liver / Q000378:metabolism*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D010088:Oxidoreductases / Q000097:blood; D044925:Oxidoreductases Acting on CH-CH Group Donors; D012510:Sarcoma 180 / Q000378:metabolism*
D010088:Oxidoreductases; D044925:Oxidoreductases Acting on CH-CH Group Donors; D050744:Dihydrouracil Dehydrogenase (NAD+); D005472:Fluorouracil