Pharmaceutical Development, AbbVie Inc., North Chicago, IL, USA.
Orlando Clinical Research Center, Orlando, FL, USA.
Clin Pharmacol Drug Dev. 2019 Nov;8(8):1053-1061. doi: 10.1002/cpdd.640. Epub 2018 Dec 20.
The aim of these studies was to assess the safety and pharmacokinetics of elagolix, an oral nonpeptide gonadotropin-releasing hormone antagonist following oral administration in women with renal or hepatic impairment. Two phase 1 studies were conducted in adult women with normal renal function versus renal impairment (reduced study), and normal hepatic function versus hepatic impairment (full study design). All women received a single dose of elagolix 200 mg (renal) or 150 mg (hepatic). Intensive pharmacokinetic blood samples were collected. Elagolix exposures were comparable in women with normal renal function and those with moderate/severe renal impairment or end-stage renal disease. Elagolix exposures also appeared to be similar in women with normal hepatic function and women with mild hepatic impairment. Elagolix area under the curve in women with moderate hepatic impairment and with severe hepatic impairment was approximately 3-fold and 7-fold higher than in women with normal hepatic function. The adverse event incidence was low, with the main events being mild nausea and headache. No dosage adjustment was needed in women with renal impairment or women with mild hepatic impairment. Although an elagolix dose of 150 mg once daily may be used in women with moderate hepatic impairment for up to 6 months, this elagolix dose should not be used in women with severe hepatic impairment.
这些研究的目的是评估口服非肽类促性腺激素释放激素拮抗剂依戈洛克斯在有肾或肝损伤的女性中的安全性和药代动力学。在肾功能正常的成年女性与肾功能损伤（降低研究）和肝功能正常的成年女性与肝功能损伤（完整研究设计）中进行了两项 1 期研究。所有女性均接受单次 200mg 依戈洛克斯（肾）或 150mg 依戈洛克斯（肝）剂量治疗。采集密集型药代动力学血样。肾功能正常的女性与中度/重度肾功能损伤或终末期肾病女性的依戈洛克斯暴露情况相当。肝功能正常的女性与轻度肝功能损伤女性的依戈洛克斯暴露情况也似乎相似。中度肝功能损伤和重度肝功能损伤女性的依戈洛克斯曲线下面积（AUC）分别比肝功能正常女性高约 3 倍和 7 倍。不良事件发生率较低，主要事件为轻度恶心和头痛。肾功能损伤或轻度肝功能损伤的女性无需调整剂量。尽管对于中度肝功能损伤的女性，每日一次使用 150mg 依戈洛克斯可能最长使用 6 个月，但不应在重度肝功能损伤的女性中使用该剂量。
