Erschienen in:
23.02.2018 | Original Research Article
Population Pharmacokinetics of Elagolix in Healthy Women and Women with Endometriosis
verfasst von:
Insa Winzenborg, Ahmed Nader, Akshanth R. Polepally, Mohan Liu, Jacob Degner, Cheri E. Klein, Nael M. Mostafa, Peter Noertersheuser, Juki Ng
Erschienen in:
Clinical Pharmacokinetics
|
Ausgabe 10/2018
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Abstract
Introduction
Elagolix is a novel, orally active, non-peptide, competitive gonadotropin-releasing hormone (GnRH) receptor antagonist in development for the management of endometriosis with associated pain and heavy menstrual bleeding due to uterine fibroids. The pharmacokinetics of elagolix have been well-characterized in phase I studies; however, elagolix population pharmacokinetics have not been previously reported. Therefore, a robust model was developed to describe elagolix population pharmacokinetics and to evaluate factors affecting elagolix pharmacokinetic parameters.
Methods
The data from nine clinical studies (a total of 1624 women) were included in the analysis: five phase I studies in healthy, premenopausal women and four phase III studies in premenopausal women with endometriosis.
Results
Elagolix population pharmacokinetics were best described by a two-compartment model with a lag time in absorption. Of the 15 covariates tested for effect on elagolix apparent clearance (CL/F) and/or volume of distribution only one covariate, organic anion transporting polypeptide (OATP) 1B1 genotype status, had a statistically significant, but not clinically meaningful, effect on elagolix CL/F.
Conclusion
Elagolix pharmacokinetics were not affected by patient demographics and were similar between healthy women and women with endometriosis.
Clinical Trial Registration Numbers NCT01403038, NCT01620528, NCT01760954, NCT01931670, NCT02143713.