AbbVie, Madison, New Jersey, USA.
Clin Pharmacol Drug Dev. 2021 Jul;10(7):726-733. doi: 10.1002/cpdd.916. Epub 2021 Jan 27.
Atogepant is a selective oral calcitonin gene-related peptide receptor antagonist in development for migraine prevention. Here, we report the pharmacokinetics (PK) and safety of single-dose 60 mg atogepant in participants with severe, moderate, or mild hepatic impairment and matched participants with normal hepatic function from an open-label, parallel-group, single-dose phase 1 trial. Thirty-two participants aged 45 to 72 years were enrolled, which included 8 each with severe, moderate, mild, or no hepatic impairment. All participants completed the study. Atogepant was rapidly absorbed (median time to maximum plasma concentration, ∼2 hours) with an apparent terminal elimination half-life of ∼11 hours. Compared with participants with normal hepatic function, the change in maximum plasma concentrations of atogepant were -4%, -12%, and +9% in participants with severe, moderate, or mild hepatic impairment, respectively. Overall systemic exposures to atogepant were 15% to 38% higher in participants with hepatic impairment compared with those with normal hepatic function, but these differences are not expected to be clinically relevant given the established safety profile of atogepant. Only 1 adverse event was reported: mild rhinorrhea in a participant with moderate hepatic impairment. Overall, atogepant was safe and not associated with any clinically relevant change in PK in participants with severe, moderate, or mild hepatic impairment.
阿替利珠单抗是一种正在开发用于偏头痛预防的选择性口服降钙素基因相关肽受体拮抗剂。在此，我们报告了一项开放标签、平行组、单次剂量 1 期临床试验中，60 毫克单剂量阿托格潘在严重、中度或轻度肝损伤以及匹配的肝功能正常参与者中的药代动力学（PK）和安全性。共有 32 名年龄在 45 至 72 岁的参与者入组，其中包括 8 名严重、中度、轻度或无肝损伤的参与者。所有参与者均完成了研究。阿托格潘吸收迅速（最大血浆浓度的中位时间约为 2 小时），表观终末消除半衰期约为 11 小时。与肝功能正常的参与者相比，严重、中度或轻度肝损伤的参与者的阿托格潘最大血浆浓度变化分别为-4%、-12%和+9%。与肝功能正常的参与者相比，肝损伤参与者的阿托格潘总体全身暴露量高 15%至 38%，但鉴于阿托格潘已确立的安全性概况，这些差异预计不会具有临床相关性。仅有 1 例不良事件报告：1 例中度肝损伤患者出现轻度鼻漏。总体而言，阿托格潘在严重、中度或轻度肝损伤患者中是安全的，且与 PK 无任何临床相关变化相关。
