Thalidomide does not alter the pharmacokinetics of ethinyl estradiol and norethindrone

Citation
Cb. Trapnell et al., Thalidomide does not alter the pharmacokinetics of ethinyl estradiol and norethindrone, CLIN PHARM, 64(6), 1998, pp. 597-602
Citations number
27
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Pharmacology,"Pharmacology & Toxicology
Journal title
CLINICAL PHARMACOLOGY & THERAPEUTICS
ISSN journal
0009-9236 → ACNP
Volume
64
Issue
6
Year of publication
1998
Pages
597 - 602
Database
ISI
SICI code
0009-9236(199812)64:6<597:TDNATP>2.0.ZU;2-4
Abstract
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.