Thalidomide does not alter the pharmacokinetics of ethinyl estradiol and norethindrone.
OBJECTIVE
To evaluate the effect of thalidomide on the plasma pharmacokinetics of ethinyl estradiol (INN, ethinylestradiol) and norethindrone (INN, norethisterone).


METHODS
Ten women who had undergone surgical sterilization were enrolled in an open-label crossover study conducted in the Georgetown University Clinical Research Center. The pharmacokinetics of single doses of 0.07 mg ethinyl estradiol and 2 mg norethindrone were measured at baseline and after 3 weeks of 200 mg thalidomide. Compliance with the thalidomide regimen was assessed with use of Medication Event Monitoring System (MEMS) caps.


RESULTS
No changes were observed in the pharmacokinetics of ethinyl estradiol or norethindrone with thalidomide therapy. The mean +/- SD area under the plasma concentration-time curve (AUC0-infinity) for ethinyl estradiol was 6580 +/- 1100 ng.h/L at baseline and 5970 +/- 1560 ng.h/L after the thalidomide regimen (paired t test, P > .05). The values for norethindrone were 103 +/- 54 micrograms.h/L and 107 +/- 58 micrograms.h/L (paired t test, P > .05). No changes were observed for other pharmacokinetic parameters assessed for either ethinyl estradiol or norethindrone. No accumulation of thalidomide was seen after 21 days of therapy: day 1 AUC0-infinity 41.1 +/- 13.9 micrograms.h/mL; day 21 AUC0-infinity 59.6 +/- 27.3 micrograms.h/mL (paired t test, P > .05). No changes were observed for other pharmacokinetic parameters assessed for thalidomide between days 1 and 21. Thalidomide was well tolerated but caused variable degrees of sedation. The average thalidomide compliance rate was 97%.


CONCLUSIONS
The pharmacokinetics of thalidomide do not change with 3 weeks of daily dosing. Thalidomide does not alter the pharmacokinetics of ethinyl estradiol or norethindrone. Therefore there is no drug interaction between thalidomide and these 2 drugs. The efficacy of oral contraceptives containing ethinyl estradiol and norethindrone should not be affected by concomitant thalidomide therapy.
Trapnell
C B
CB
Food and Drug Administration, Rockville, USA. trapnelc@globomax.com
Donahue
S R
SR
Collins
J M
JM
Flockhart
D A
DA
Thacker
D
D
Abernethy
D R
DR
D000328:Adult; D019540:Area Under Curve; D003280:Contraceptives, Oral, Synthetic / Q000097:blood / Q000493:pharmacokinetics*; D018592:Cross-Over Studies; D045166:Estradiol Congeners / Q000097:blood / Q000493:pharmacokinetics*; D004997:Ethinyl Estradiol / Q000097:blood / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D008875:Middle Aged; D009640:Norethindrone / Q000097:blood / Q000493:pharmacokinetics*; D045167:Progesterone Congeners / Q000097:blood / Q000493:pharmacokinetics*; D013792:Thalidomide / Q000494:pharmacology*
D003280:Contraceptives, Oral, Synthetic; D045166:Estradiol Congeners; D007166:Immunosuppressive Agents; D045167:Progesterone Congeners; D004997:Ethinyl Estradiol; D013792:Thalidomide; D009640:Norethindrone