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- Title
Population Pharmacokinetics of Elagolix in Healthy Women and Women with Endometriosis.
- Authors
Winzenborg, Insa; Nader, Ahmed; Polepally, Akshanth R.; Liu, Mohan; Degner, Jacob; Klein, Cheri E.; Mostafa, Nael M.; Noertersheuser, Peter; Ng, Juki
- Abstract
<bold>Introduction: </bold>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.<bold>Methods: </bold>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.<bold>Results: </bold>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.<bold>Conclusion: </bold>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.
- Subjects
ENDOMETRIOSIS; DISEASES in women; PHARMACOKINETICS; UTERINE fibroids; PERIMENOPAUSE; BIOLOGICAL models; RESEARCH; CLINICAL trials; HETEROCYCLIC compounds; RESEARCH methodology; CELL receptors; EVALUATION research; MEDICAL cooperation; COMPARATIVE studies; GENOTYPES; FLUOROHYDROCARBONS; BIOTRANSFORMATION (Metabolism)
- Publication
Clinical Pharmacokinetics, 2018, Vol 57, Issue 10, p1295
- ISSN
0312-5963
- Publication type
journal article
- DOI
10.1007/s40262-018-0629-6