Kinetics of drug action in disease states. XXII. Effects of contraceptive steroids on the pharmacodynamics of ethanol in rats.

This investigation was designed to determine the effect of treatment with contraceptive steroids on the central nervous system depressant activity of ethanol. Adult female rats received oral doses of ethynyl estradiol (0.1 mg kg-1 day-1), ethynyl estradiol and norethindrone (0.1 and 10 mg kg-1 day-1), or vehicle only for 14 days. Ethanol was then infused slowly iv until the animals lost their righting reflex. The concentrations of ethanol at that time in serum and cerebrospinal fluid were statistically significantly higher in rats treated with the estrogen-progestin combination than in control animals. Ethanol concentrations in rats treated only with the estrogen were intermediate and did not differ significantly from control values. These results indicate that treatment with an estrogen-progestin combination is associated with a decreased sensitivity of the central nervous system to the hypnotic activity of ethanol. This evidence of a pharmacodynamic interaction between contraceptive steroids and ethanol in rats is consistent with a recent clinical report of significant contraceptive steroid-related improvement in tolerance to ethanol with no apparent effect on the pharmacokinetics of ethanol.