Estimating systemic exposure to ethinyl estradiol from an oral contraceptive - 27/04/15
, Malcolm C. Pike, PhD d, Rosalind Tang, MS b, Marianne N. DiNapoli, MD b, Monica Sull, MPH b, Serge Cremers, PharmD, PhD cAbstract |
Objective |
This study was conducted to compare single-dose pharmacokinetics of ethinyl estradiol in an oral contraceptive with steady-state values and to assess whether any simpler measures could provide an adequate proxy of the “gold standard” 24-hour steady-state area under the curve (AUC) value. Identification of a simple, less expensive measure of systemic ethinyl estradiol exposure would be useful for larger studies that are designed to assess the relationship between an individual’s ethinyl estradiol exposure and side-effects.
Study Design |
We collected 13 samples over 24 hours for pharmacokinetic analysis on days 1 and 21 of the first cycle of a monophasic oral contraceptive that contained 30 μg ethinyl estradiol and 150 μg levonorgestrel in 17 nonobese healthy white women. We also conducted an abbreviated single-dose 9-sample pharmacokinetic analysis after a month washout. Ethinyl estradiol was measured by liquid chromatography-tandem mass spectrometry. We compared results of a full 13-sample steady-state pharmacokinetic analysis with results that had been calculated with the use of fewer samples (9 or 5) and after the single doses. We calculated Pearson correlation coefficients to evaluate the relationships between these estimates of systemic ethinyl estradiol exposure.
Results |
The AUC, maximum, and 24-hour values were similar after the 2 single oral contraceptive doses (AUC; r = 0.92). The steady-state 13-sample 24-hour AUC value was correlated highly with the average 9-sample AUC value after the 2 single doses (r = 0.81; P = .0002). This correlation remained the same if the number of single-dose samples was reduced to 4, taken at time 1, 2.5, 4, and 24 hours. The 24-hour value at steady-state was correlated highly with the 24-hour steady-state AUC value (r = 0.92; P < .0001). The average of the 24-hour values after the 2 single doses was also correlated quite highly with the steady-state AUC value (r = 0.72; P = .0026).
Conclusion |
Limited blood sampling, including results from 2 single doses, gave highly correlated estimates of an oral contraceptive user’s steady-state ethinyl estradiol exposure.
Le texte complet de cet article est disponible en PDF.Key words : ethinyl estradiol, oral contraceptive, pharmacokinetics, single-dose, steady-state
Plan
| This pilot study was funded by the Howard Solomon Research Fund of the Department of Obstetrics and Gynecology, Columbia University Medical Center (CUMC), and the Irving Institute for Clinical and Translational Research Collaborative and Multidisciplinary Pilot Research Award from CUMC. The CUMC Biomarkers Core Laboratory supported the ethinyl estradiol assays. This publication was supported by the National Center for Advancing Translational Sciences, National Institutes of Health, through grant number UL1 TR000040, formerly the National Center for Research Resources, grant number UL1 RR024156. |
|
| The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. |
|
| C.L.W. is a paid consultant to Merck and Bayer, which manufactures oral contraceptives, not the oral contraceptive evaluated in this study. The remaining authors report no conflict of interest. |
|
| Cite this article as: Westhoff CL, Pike MC, Tang R, et al. Estimating systemic exposure to ethinyl estradiol from an oral contraceptive. Am J Obstet Gynecol 2015;212:614.e1-7. |
Vol 212 - N° 5
P. 614.e1-614.e7 - mai 2015 Retour au numéro
Article précédent
- Colonization of the upper genital tract by vaginal bacterial species in nonpregnant women
- Caroline M. Mitchell, Anoria Haick, Evangelyn Nkwopara, Rochelle Garcia, Mara Rendi, Kathy Agnew, David N. Fredricks, David Eschenbach
- Depressive symptoms and risk of uterine leiomyomata
- Lauren A. Wise, Se Li, Julie R. Palmer, Lynn Rosenberg
Bienvenue sur EM-consulte, la référence des professionnels de santé.
L’accès au texte intégral de cet article nécessite un abonnement.
Déjà abonné à cette revue ?