Thalidomide does not alter the pharmacokinetics of ethinyl estradiol and norethindrone

Objective: To evaluate the effect of thalidomide on the plasma pharmacokine tics of ethinyl estradiol (INN, ethinylestradiol) and norethindrone (PNN, n orethisterone), Methods: Ten women who had undergone surgical sterilization were enrolled i n an open-label crossover study conducted in the Georgetown University Clin ical Research Center. The pharmacokinetics of single doses of 0.07 mg ethin yl estradiol and 2 mg norethindrone were measured at baseline and after 3 w eeks of 200 mg thalidomide. Compliance with the thalidomide regimen was ass essed with use of Medication Event Monitoring System (MEMS) caps. Results: No changes were observed in the pharmacokinetics of ethinyl estrad iol or norethindrone with thalidomide therapy. The mean +/- SD area under t he plasma concentration-time curve (AUC(0-infinity)) for ethinyl estradiol was 6580 +/- 1100 ng.h/L at baseline and 5970 +/- 1560 ng h/L after the tha lidomide regimen (paired t test, P > .05), The values for norethindrone wer e 103 +/- 54 mu g h/L and 107 +/- 58 mu g.h/L (paired t test, P > .05), No changes were observed for other pharmacokinetic parameters assessed for eit her ethinyl estradiol or norethindrone. No accumulation of thalidomide was seen after 21 days of therapy: day 1 AUC(0-infinity) 41.1 +/- 13.9 mu g.h/m L; day 21 AUC(0-infinity) 59.6 +/- 27.3 mu g.h/mL, (paired t test, P > .05) , No changes were observed for other pharmacokinetic parameters assessed fo r thalidomide between days 1 and 21, Thalidomide was well tolerated but cau sed variable degrees of sedation. The average thalidomide compliance rate w as 97%, Conclusions: The pharmacokinetics of thalidomide do not change with 3 weeks of daily dosing. Thalidomide does not alter the pharmacokinetics of ethiny l estradiol or norethindrone. Therefore there is no drug interaction betwee n thalidomide and these 2 drugs. The efficacy of oral contraceptives contai ning ethinyl estradiol and norethindrone should not be affected by concomit ant thalidomide therapy.