Population Pharmacokinetics of Elagolix in Healthy Women and Women with Endometriosis

Clin Pharmacokinet. 2018 Oct;57(10):1295-1306. doi: 10.1007/s40262-018-0629-6.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Clinical Trials, Phase I as Topic
  • Clinical Trials, Phase III as Topic
  • Endometriosis / drug therapy
  • Endometriosis / metabolism*
  • Female
  • Genotype
  • Humans
  • Hydrocarbons, Fluorinated / pharmacokinetics*
  • Inactivation, Metabolic
  • Liver-Specific Organic Anion Transporter 1 / genetics
  • Models, Biological*
  • Premenopause / metabolism*
  • Pyrimidines / pharmacokinetics*
  • Receptors, LHRH / antagonists & inhibitors


  • Hydrocarbons, Fluorinated
  • Liver-Specific Organic Anion Transporter 1
  • Pyrimidines
  • Receptors, LHRH
  • SLCO1B1 protein, human
  • elagolix

Associated data

  • ClinicalTrials.gov/NCT01403038
  • ClinicalTrials.gov/NCT01620528
  • ClinicalTrials.gov/NCT01760954
  • ClinicalTrials.gov/NCT01931670
  • ClinicalTrials.gov/NCT02143713