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.
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D000983:Antipyrine / Q000378:metabolism*; D001189:Aryl Hydrocarbon Hydroxylases / Q000032:analysis; D003577:Cytochrome P-450 Enzyme System / Q000032:analysis; D066298:In Vitro Techniques; D007408:Intestinal Absorption / Q000187:drug effects; D007700:Kinetics; D008297:Male; D008657:Metabolic Clearance Rate / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D014802:Vitamin A Deficiency / Q000378:metabolism*
D000970:Antineoplastic Agents; D003577:Cytochrome P-450 Enzyme System; D001189:Aryl Hydrocarbon Hydroxylases; D000983:Antipyrine