Thalidomide does not alter the pharmacokinetics of ethinyl estradiol and norethindrone

Carol Braun Trapnell, Stephen R. Donahue, Jerry M. Collins, David A. Flockhart, David Thacker, Darrell R. Abernethy

Research output: Contribution to journalArticle

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Abstract

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 (AUC(0-≡)) for ethinyl estradiol was 6580 ± 1100 ng · h/L at baseline and 5970 ± 1560 ng · h/T, after the thatalidomide deregimen (paired t test, P > .05). The values for norethindrone were 103 ± 54 μg · h/L and 107 ± 58 μg · 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 AUC(0-≡) 41.1 ± 13.9 μg · h/mL; day 21 AUC(0-≡) 59.6 ± 27.3 μg · 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.

Original languageEnglish (US)
Pages (from-to)597-602
Number of pages6
JournalClinical Pharmacology and Therapeutics
Volume64
Issue number6
DOIs
StatePublished - Dec 1998
Externally publishedYes

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Norethindrone
Ethinyl Estradiol
Thalidomide
Pharmacokinetics
Area Under Curve
Oral Contraceptives
Drug Interactions
Cross-Over Studies
Therapeutics

ASJC Scopus subject areas

  • Pharmacology

Cite this

Trapnell, C. B., Donahue, S. R., Collins, J. M., Flockhart, D. A., Thacker, D., & Abernethy, D. R. (1998). Thalidomide does not alter the pharmacokinetics of ethinyl estradiol and norethindrone. Clinical Pharmacology and Therapeutics, 64(6), 597-602. https://doi.org/10.1016/S0009-9236(98)90050-9

Thalidomide does not alter the pharmacokinetics of ethinyl estradiol and norethindrone. / Trapnell, Carol Braun; Donahue, Stephen R.; Collins, Jerry M.; Flockhart, David A.; Thacker, David; Abernethy, Darrell R.

In: Clinical Pharmacology and Therapeutics, Vol. 64, No. 6, 12.1998, p. 597-602.

Research output: Contribution to journalArticle

Trapnell, CB, Donahue, SR, Collins, JM, Flockhart, DA, Thacker, D & Abernethy, DR 1998, 'Thalidomide does not alter the pharmacokinetics of ethinyl estradiol and norethindrone', Clinical Pharmacology and Therapeutics, vol. 64, no. 6, pp. 597-602. https://doi.org/10.1016/S0009-9236(98)90050-9
Trapnell, Carol Braun ; Donahue, Stephen R. ; Collins, Jerry M. ; Flockhart, David A. ; Thacker, David ; Abernethy, Darrell R. / Thalidomide does not alter the pharmacokinetics of ethinyl estradiol and norethindrone. In: Clinical Pharmacology and Therapeutics. 1998 ; Vol. 64, No. 6. pp. 597-602.
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abstract = "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 (AUC(0-≡)) for ethinyl estradiol was 6580 ± 1100 ng · h/L at baseline and 5970 ± 1560 ng · h/T, after the thatalidomide deregimen (paired t test, P > .05). The values for norethindrone were 103 ± 54 μg · h/L and 107 ± 58 μg · 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 AUC(0-≡) 41.1 ± 13.9 μg · h/mL; day 21 AUC(0-≡) 59.6 ± 27.3 μg · 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.",
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T1 - Thalidomide does not alter the pharmacokinetics of ethinyl estradiol and norethindrone

AU - Trapnell, Carol Braun

AU - Donahue, Stephen R.

AU - Collins, Jerry M.

AU - Flockhart, David A.

AU - Thacker, David

AU - Abernethy, Darrell R.

PY - 1998/12

Y1 - 1998/12

N2 - 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 (AUC(0-≡)) for ethinyl estradiol was 6580 ± 1100 ng · h/L at baseline and 5970 ± 1560 ng · h/T, after the thatalidomide deregimen (paired t test, P > .05). The values for norethindrone were 103 ± 54 μg · h/L and 107 ± 58 μg · 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 AUC(0-≡) 41.1 ± 13.9 μg · h/mL; day 21 AUC(0-≡) 59.6 ± 27.3 μg · 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.

AB - 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 (AUC(0-≡)) for ethinyl estradiol was 6580 ± 1100 ng · h/L at baseline and 5970 ± 1560 ng · h/T, after the thatalidomide deregimen (paired t test, P > .05). The values for norethindrone were 103 ± 54 μg · h/L and 107 ± 58 μg · 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 AUC(0-≡) 41.1 ± 13.9 μg · h/mL; day 21 AUC(0-≡) 59.6 ± 27.3 μg · 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.

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