Pharmacokinetics of single and multiple doses of ethinyl estradiol and levonorgestrel in relation to smoking.

ABSTRACT

PIP: The effects of combined cigarette smoking and oral contraceptive (OC) use on the pharmacokinetics of the pill's major components were examined in 27 white female volunteers grouped as follows: Group 1, non-OC user, nonsmoker; Group 2, OC user, nonsmoker; Group 3, non-OC user, smoker; Group 4, OC user, smoker. The 11 OC users in the study had been taking the pill for over 6 months; 5 were taking Ovral (50 mcg of ethinyl estradiol, 0.5 mg of norgestrel) and the remaining 6 switched to Ovral for the 1-month cycle before the study period. The non-OC users took 1 study dose of Ovral. The clearance of levonorgestrel was significantly lower in chronic OC users (mean elimination half-life of 30 hours) than in single-dose subjects (mean elimination half-life of 23 hours). The mean elimination half-life of ethinyl estradiol was approximately 12 hours for both chronic and acute OC use, although there was a nonsignificant tendency for lower ethinyl estradiol clearances in chronic OC users. Chronic tobacco use as a single factor did not influence the pharmacokinetics of levonorgestrel; however, a joint effect from chronic OC use and tobacco use was seen for ethinyl estradiol. Tobacco use had no effect on steroid pharmacokinetics in the non-OC users. Finally, a linear relationship was found between 24-hour trough serum concentrations and area-under-curve values of both steroids that may facilitate population monitoring studies of OC exposure.