The effect of anti-cancer drugs on pharmacokinetics of antipyrine in vitamin A deficiency.

The pharmacokinetics of orally and intravenously administered antipyrine-14C in individual rats were investigated to examine the effects of vitamin A deficiency and/or cytotoxic anti-cancer drugs, like cyclophosphamide, methotrexate, 5-fluorouracil and actinomycin-D. Both vitamin A deficiency and pretreatment of rats with anti-cancer drugs led to impairment in the absorption from the gastro-intestinal tract and the plasma elimination of antipyrine. Pretreatment of vitamin A deficient rats with anti-cancer drugs further retarded the absorption and plasma clearance of antipyrine. Apparent volume of distribution of antipyrine was reduced (P less than 0.001) by inducing vitamin A deficiency in rats, whereas pretreatment of rats with anti-cancer drugs did not show any effect. Cytotoxic drugs, and vitamin A deficiency increased the area under the plasma concentration vs. time curve of orally administered antipyrine (AUCoral). In vitro findings suggest that the most probable cause of delayed clearance/prolonged half-life and increased AUCoral values was the reduction in hepatic cytochrome P-450 dependent mixed function oxidase system.