Inhibition of Hepatic Drug Metabolism by Anticancer Agents

Abstract

Pretreatment of the rats with methotrexate, cyclophosphamide and 5-fluorouracil could cause inhibition of hepatic drug metabolism of zoxazolamine, aminopyrine and aniline, as evidenced by a prolongation of zoxazolamine paralysis time and a decrease in the elimination of the latter two amines from the plasma. However, the rate of absorption of both aminopyrine and aniline were unaffected. In vitro investigations were consistent with the view that the most likely cause of this inhibited hepatic drug metabolism produced by these anticancer agents was the reduction in one or more components of the drug-metabolizing enzyme system, including the cytochrome P450 content.