Abstract：
Rimegepant is a small-molecule calcitonin gene-related peptide receptor antagonist (gepant) with demonstrated efficacy and safety in the acute and preventive treatment of migraine. Here, we report the pharmacokinetics and safety of a single 75-mg oral dose of rimegepant in subjects with severe, moderate, or mild hepatic impairment and matched healthy subjects from an open-label, single-dose, 4-group phase 1 study. Thirty-six subjects aged 41-71 years were enrolled, including 6 each with severe, moderate, or mild hepatic impairment and 18 healthy subjects. All subjects completed the study. A <20% increase in total and unbound pharmacokinetics was observed in subjects with mild hepatic impairment and ≤65% increase with moderate hepatic impairment versus matched healthy controls. Total and unbound systemic exposure increased 2.0- and 3.9-fold in the severe hepatic impairment group. In subjects with severe hepatic impairment, geometric mean ratios (severe impairment/controls) for total concentrations were 202.2% for area under the plasma concentration-time curve from time 0 to the last quantifiable concentration, 202.2% for area under the plasma concentration-time curve from time 0 to infinity, and 189.1% for maximum observed plasma concentration. Corresponding geometric mean ratios using unbound concentrations were 388.8% and 388.7%, respectively. Three (8.3%) subjects reported 4 treatment-emergent adverse events. Rimegepant is not recommended for use in adults with severe hepatic impairment.
摘要：
Rimegepant是一种小分子降钙素基因相关肽受体拮抗剂（gepant），在偏头痛的急性和预防性治疗中具有良好的疗效和安全性。这里,我们报告了单次75mg口服剂量的Rimegepant在患有严重，中度,或轻度肝功能损害和来自开放标签的匹配健康受试者，单剂量,4组1期研究。纳入36名年龄在41-71岁的受试者，包括严重的6个，中度,或轻度肝功能损害和18名健康受试者。所有受试者完成研究。与匹配的健康对照相比，在轻度肝功能损害的受试者中观察到总的和未结合的药代动力学增加<20％，中度肝功能损害的受试者增加≤65％。在严重肝功能损害组中，总的和未结合的全身暴露增加了2.0倍和3.9倍。在患有严重肝功能损害的受试者中，从时间0到最后一个可量化浓度的血浆浓度-时间曲线下面积的几何平均比率（严重损伤/对照）为202.2%，从时间0到无穷大的血浆浓度-时间曲线下面积为202.2%，观察到的最大血浆浓度为189.1％。使用未结合浓度的相应几何平均比率为388.8％和388.7％，分别。三名（8.3％）受试者报告了4起治疗引起的不良事件。Rimegepant不推荐用于患有严重肝功能损害的成人。
