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

Abstract

The effects of tobacco and oral contraceptive (OC) use (Ovral) on the pharmacokinetics of levonorgestrel (0.25 mg) and ethinyl estradiol (50 micrograms) were examined. Young women (n = 27) were grouped as follows: I: non-OC users/nonsmokers; II: OC users/nonsmokers; III: non-OC users/smokers; and IV: OC users/smokers. The apparent clearance of levonorgestrel in group I was 80.9 +/- 15.6 ml/hr/kg and the half-life was 19.3 hours. A significant decrease in levonorgestrel clearance was seen in the chronic OC users (groups II and IV). The apparent oral clearance of ethinyl estradiol was 1002 +/- 398 ml/hr/kg in group I and the half-life averaged 7.7 hours. Groups II and III showed decreased (not significant) clearance of ethinyl estradiol. Tobacco use had no effect on steroid pharmacokinetics in the non-OC users. Although chronic OC use did not affect ethinyl estradiol clearance, a joint effect of tobacco/OC use on enhancing clearance of ethinyl estradiol appeared to occur. A linear relationship was found between 24-hour trough serum concentrations and AUC values of both steroids that may facilitate population monitoring studies of OC exposure.

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.