Abstract | BACKGROUND AND OBJECTIVES: METHODS: Data from 13 clinical studies (a total of 2168 women) consisting of six phase I studies in healthy premenopausal women, four phase III studies in premenopausal women with endometriosis, and three phase III studies in premenopausal women with uterine fibroids were analyzed using a non-linear mixed-effects modeling approach. RESULTS:
Elagolix population pharmacokinetics was best described by a two-compartment model with first-order absorption, lag time in absorption, and first-order elimination. Out of the covariates tested on elagolix apparent clearance, apparent volume of distribution, and/or relative bioavailability, only organic anion transporting polypeptide 1B1 genotype status and body weight had a statistically significant but no clinically meaningful effect on elagolix relative bioavailability and apparent volume of distribution, respectively. There were no clinically meaningful differences in elagolix population pharmacokinetics in healthy women or women with endometriosis or uterine fibroids. CONCLUSIONS: CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov identifiers: NCT01620528 (EM-1), NCT01760954 (EM-1-Extend), NCT01931670 (EM-2), NCT02143713 (EM-2-Extend), NCT02654054 (UF-1), NCT02691494 (UF-2), NCT0295494 (UF-Extend).
|
Authors | Denise Beck, Insa Winzenborg, Mohan Liu, Jacob Degner, Nael M Mostafa, Peter Noertersheuser, Mohamad Shebley |
Journal | Clinical pharmacokinetics
(Clin Pharmacokinet)
Vol. 61
Issue 4
Pg. 577-587
(04 2022)
ISSN: 1179-1926 [Electronic] Switzerland |
PMID | 34878624
(Publication Type: Journal Article)
|
Copyright | © 2021. The Author(s). |
Chemical References |
- Hydrocarbons, Fluorinated
- Pyrimidines
- Gonadotropin-Releasing Hormone
- Estradiol
- elagolix
- Norethindrone Acetate
|
Topics |
- Clinical Trials, Phase III as Topic
- Estradiol
(therapeutic use)
- Female
- Gonadotropin-Releasing Hormone
- Humans
- Hydrocarbons, Fluorinated
- Leiomyoma
(complications, drug therapy)
- Norethindrone Acetate
- Pyrimidines
|