Li Cuiyun, Mai Jiajia, Wu Min, Zhang Hong, Li Xiaojiao, Li Haijun, Li Youyun, Ding Yanhua
Phase I Clinical Trial Unit, First Hospital, Jilin University, Changchun, China.
Department of Anatomy and Neurobiology, School of Basic Medical Sciences, Central South University, Changsha, China.
Antimicrob Agents Chemother. 2025 Feb 13;69(2):e0137724. doi: 10.1128/aac.01377-24. Epub 2024 Dec 17.
This study evaluated the safety and pharmacokinetics (PK) of a single dose of leritrelvir, a novel inhibitor of 3-chymotrypsin-like cysteine protease (3CLpro), in patients with hepatic impairment versus healthy participants with normal hepatic function. Eight participants with mild (Child-Pugh A) hepatic impairment, eight with moderate (Child-Pugh B) hepatic impairment, and eight healthy matched control participants were enrolled in this open-label, parallel clinical trial. After administration of leritrelvir of 400 mg, PK parameters were calculated and compared across groups. In total, 24 participants were enrolled and completed the study. Leritrelvir was generally well tolerated, with no serious adverse events or deaths reported during the study. Compared to the group with normal hepatic function, the geometric least-squares mean ratios (90% confidence intervals) for , AUC, and AUC of leritrelvir in participants with mild hepatic impairment were 96.9% (69.3%, 135%), 92.2% (69.6%, 122%), and 92.1% (69.7%, 122%), respectively. For moderate hepatic impairment, the corresponding ratios were 91.6% (61.7%, 136%), 113% (80.0%, 160%), and 113% (80.0%, 159%). Leritrelvir exposures were comparable among the three groups. Overall, there was no clinically relevant difference in leritrelvir exposure in participants with hepatic impairment compared to normal controls. No dose adjustment is required for leritrelvir in patients with mild or moderate hepatic impairment.CLINICAL TRIALSThis study is registered with ClinicalTrials.gov as NCT06161259.
本研究评估了新型3 - 糜蛋白酶样半胱氨酸蛋白酶（3CLpro）抑制剂单剂量来瑞特韦在肝功能损害患者与肝功能正常的健康参与者中的安全性和药代动力学（PK）。八名轻度（Child - Pugh A级）肝功能损害参与者、八名中度（Child - Pugh B级）肝功能损害参与者以及八名健康匹配对照参与者被纳入这项开放标签、平行的临床试验。在给予400 mg来瑞特韦后，计算并比较了各组的PK参数。共有24名参与者被纳入并完成了研究。来瑞特韦总体耐受性良好，研究期间未报告严重不良事件或死亡。与肝功能正常组相比，轻度肝功能损害参与者中来瑞特韦的 、AUC和AUC的几何最小二乘均值比（90%置信区间）分别为96.9%（69.3%，135%）、92.2%（69.6%，122%）和92.1%（69.7%，122%）。对于中度肝功能损害，相应的比值分别为91.6%（61.7%，136%）、113%（80.0%，`160%）和113%（80.0%，159%）。三组中来瑞特韦的暴露量相当。总体而言，与正常对照组相比，肝功能损害参与者中来瑞特韦的暴露量在临床上无显著差异。轻度或中度肝功能损害患者使用来瑞特韦无需调整剂量。临床试验本研究已在ClinicalTrials.gov注册，注册号为NCT06161259。
