Thalidomide does not alter estrogen-progesterone hormone single-dose pharmacokinetics

Objective: To determine the single- and multiple-dose pharmacokinetics of o ral thalidomide (200 mg/day, administered for 21 days) and to assess the ef fects of steady-state plasma concentrations of thalidomide on the single-do se pharmacokinetics of ethinyl estradiol (INN, ethinylestradiol) and noreth indrone (INN, norethisterone), Method: A randomized, 2-period crossover study was performed in 10 healthy premenopausal female volunteers. The pharmacokinetic profiles of plasma con centrations of thalidomide were evaluated with both noncompartmental and co mpartmental methods, whereas those of ethinyl estradiol and norethindrone w ere calculated with noncompartmental methods. The effects of steady-state p lasma thalidomide concentrations on the pharmacokinetics of ethinyl estradi ol and norethindrone were determined with use of an ANOVA model that includ ed treatment sequence, subject within sequence, period, and treatment as fa ctors. Results: Thalidomide plasma concentrations were best predicted by a 1-compa rtment model with first-order absorption and elimination and an absorption time-lag. There were no significant differences between pharmacokinetic par ameters for thalidomide after 1 dose and those after 18 consecutive doses. Except for a minor decrease of the elimination rate constant (k(e)) for eth inyl estradiol, coadministration of thalidomide had no significant effects on the pharmacokinetic profiles for either ethinyl estradiol or norethindro ne. The change in k(e) for ethinyl estradiol during thalidomide administrat ion was not associated with any alteration in the clearance or elimination half-life for this hormone, Conclusions: Multiple-dose pharmacokinetics of thalidomide is similar to th e single-dose profile. This study did not investigate the efficacy of the 2 1-day fixed ethinyl estradiol-norethindrone regimen, but the results sugges t that thalidomide is unlikely to affect the pharmacokinetics of orally adm inistered hormonal contraceptives.