Influence of oral contraceptives on the acute effect of amphetamine on the hepatic endoplasmic reticulum of the rat

Abstract

The interaction between amphetamine and synthetic oral contraceptive steroids have been studied in the female rat. A progestational agent, quingestanol acetate, and a standard combination contraceptive (quingestanol acetate/ethynyl estradiol) were given with and without the concurrent administration of amphetamine. Steroid treatments increased the activity of some drug-metabolizing enzymes (aminopyrine N-demethylase, coumarin3-hydroxylase, hexobarbital oxidase). Other parameters measured remained unaltered (glucose-6-phosphatase, aniline hydroxylase, cytochrome c reductase, cytochrome P 450, microsomal protein and phospholipid contents). Amphetamine treatment alone raised some drug-metabolizing enzymes (coumarin 3-hydroxylase, hexobarbital oxidase), increased microsomal phospholipid content and de novo synthesis, but elicited no effect on other enzymes measured. Amphetamine and quingestanol acetate given together significantly increased some drug metabolizing enzymes while the simultaneous treatment with combined steroids and amphetamine showed the most pronounced action. These experiments thus revealed that at least in the liver of the female rat, amphetamine elicited no overt hepatotoxicity, rather, brought about a weak inductive action of drug metabolizing enzymes. The application of steroid hormones also raised drug metabolism and the interaction between amphetamine and contraceptive steroids showed additive effects.