Obstetrics and Gynecology, Baptist Health Medical Group, 6141 Sunset Drive, Suite 401, Miami, FL, 33143, USA.
Data and Statistics, AbbVie Inc., 1 North Waukegan Road, North Chicago, IL, 60064, USA.
Clin Pharmacokinet. 2021 Aug;60(8):1003-1013. doi: 10.1007/s40262-021-00989-0. Epub 2021 Mar 22.
Two pharmacokinetic/pharmacodynamic studies were conducted to evaluate the potential drug-drug interaction between elagolix, an oral gonadotropin-releasing hormone receptor antagonist, and an oral contraceptive (ethinylestradiol [EE] 0.035 mg and norgestimate 0.18/0.215/0.25 mg) or progestin-only contraceptive (norethindrone 0.35 mg) in healthy premenopausal women.
These phase I studies used a two-period, sequential design, where period 1 included treatment with oral contraceptives, followed by period 2 with contraceptives coadministered with elagolix 150 mg once daily.
In study 1, pharmacokinetic exposures for EE in period 2 increased by 30% and the norgestimate metabolites decreased by approximately 15% when coadministered with elagolix. Mean hormone exposure appeared lower for follicle-stimulating hormone (FSH; 31%), luteinizing hormone (LH; 38%), and estradiol (E2; 16%). The percentage of women with consecutive progesterone (P) concentrations above 5 nmol/L was similar in both periods. Norethindrone pharmacokinetic exposures were comparable in both periods. The hormone exposure for LH and FSH was similar, and mean E2 exposure was 32% lower in period 2. The percentage of subjects with consecutive ovulatory P concentrations was also similar in both periods (study 2). Safety and tolerability profiles were unremarkable in both studies.
Coadministration of elagolix 150 mg once daily with oral contraceptives containing EE and norgestimate, or norethindrone, resulted in small pharmacokinetic changes in the oral contraceptive components. Similar or lower FSH, LH, and E2 exposures were observed during coadministration, with ovulatory P concentrations also comparable in both periods. The pharmacodynamic profiles of the oral contraceptives were maintained when coadministered with elagolix.
两项药代动力学/药效学研究评估了口服促性腺激素释放激素受体拮抗剂依戈洛昔与口服避孕药（炔雌醇[EE] 0.035 毫克和屈螺酮 0.18/0.215/0.25 毫克）或孕激素避孕药（左炔诺孕酮 0.35 毫克）在健康绝经前妇女中的潜在药物相互作用。
这两项 I 期研究采用两期、序贯设计，其中第 1 期为口服避孕药治疗，第 2 期为依戈洛昔 150 毫克每日一次与避孕药联合治疗。
在研究 1 中，与依戈洛昔联合应用时，EE 在第 2 期的药代动力学暴露增加了 30%，而屈螺酮代谢物减少了约 15%。促卵泡激素（FSH；31%）、促黄体生成激素（LH；38%）和雌二醇（E2；16%）的平均激素暴露水平似乎较低。两个时期的连续孕激素（P）浓度高于 5 nmol/L 的女性百分比相似。左炔诺孕酮的药代动力学暴露在两个时期相似。LH 和 FSH 的激素暴露相似，第 2 期的平均 E2 暴露水平降低了 32%。两个时期的排卵性 P 浓度连续的受试者百分比也相似（研究 2）。两个研究的安全性和耐受性概况均无明显差异。
依戈洛昔 150 毫克每日一次与含有 EE 和屈螺酮或左炔诺孕酮的口服避孕药联合应用，导致口服避孕药成分的药代动力学变化较小。联合应用时观察到类似或更低的 FSH、LH 和 E2 暴露，两个时期的排卵性 P 浓度也相似。当与依戈洛昔联合应用时，口服避孕药的药效学特征得以维持。
