Park Maria, Choi Suein, Han Sungpil, Shin Wonsuk, Kim Anhye, Han Seunghoon, Kim Bomin, Lim Yeji, Yoo Hyounggyoon
Department of Clinical Pharmacology and Therapeutics, The Catholic University of Korea Seoul St. Mary's Hospital, Seoul 06591, Korea.
Department of Pharmacology, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea.
Transl Clin Pharmacol. 2023 Dec;31(4):226-237. doi: 10.12793/tcp.2023.31.e20. Epub 2023 Dec 20.
A new sustained-release (SR) pregabalin tablet, YHD1119, was formulated for once-daily dosing. In the current study, we aimed to evaluate the pharmacokinetics of YHD1119 tablets in patients with reduced renal function. Subjects were grouped by creatinine clearance: > 60 mL/min/1.73m (Cohort A) and 30-60 mL/min/1.73m (Cohort B). Eight subjects in Cohort A received a YHD1119 75 mg tablet (Y75T) and a YHD1119 150 mg tablet (Y150T) in each period, and eight subjects in Cohort B received a Y75T. Non-compartment analysis and population pharmacokinetic analysis using a one-compartment model with first-order elimination and first-order absorption with lag time were performed. Sixteen subjects completed the study. The geometric mean ratio (GMR) (90% confidence intervals [CI]) for maximum concentration (C), and area under the concentration-time profile from 0 to the last measurable time (AUC) after Y75T of Cohort B to those of Y75T of Cohort A were 1.2273 (1.0245-1.4701), and 2.4146 (1.8142-3.2138), respectively. The GMR (90% CI) for C, and AUC after Y75T of Cohort B to those of Y150T of Cohort A were 0.6476 (0.5229-0.8021), and 1.1471 (0.8418-1.5632), respectively. Simulated steady-steady pregabalin concentrations after once-daily Y75T dosing in subjects with eGFR 45 mL/min/1.73 m were within the range of steady-state concentrations simulated after once-daily Y150T dosing in subjects with eGFR 90 mL/min/1.73 m. The total pregabalin exposure of Y75T in patients with moderate renal impairment was comparable with that of Y150T in subjects with near-normal renal function.
ClinicalTrials.gov Identifier: NCT05012436.
一种新的缓释（SR）普瑞巴林片剂YHD1119被制备用于每日一次给药。在当前研究中，我们旨在评估YHD1119片剂在肾功能减退患者中的药代动力学。受试者按肌酐清除率分组：>60 mL/min/1.73m（队列A）和30 - 60 mL/min/1.73m（队列B）。队列A中的8名受试者在每个时期接受一片75 mg的YHD1119片剂（Y75T）和一片150 mg的YHD1119片剂（Y150T），队列B中的8名受试者接受一片Y75T。进行了非房室分析以及使用具有一级消除和带滞后时间的一级吸收的一室模型的群体药代动力学分析。16名受试者完成了研究。队列B的Y75T与队列A的Y75T相比，最大浓度（C）的几何平均比值（GMR）（90%置信区间[CI]）以及从0到最后可测量时间的浓度 - 时间曲线下面积（AUC）分别为1.2273（1.0245 - 1.4701）和2.4146（1.8142 - 3.2138）。队列B的Y75T与队列A的Y150T相比，C和AUC的GMR（90%CI）分别为0.6476（0.5229 - 0.8021）和1.1471（0.8418 - 1.5632）。估算肾小球滤过率（eGFR）为45 mL/min/1.73 m的受试者每日一次服用Y75T后的稳态普瑞巴林浓度在eGFR为90 mL/min/1.73 m的受试者每日一次服用Y150T后模拟的稳态浓度范围内。中度肾功能损害患者中Y75T的普瑞巴林总暴露量与肾功能接近正常受试者中Y150T的相当。
ClinicalTrials.gov标识符：NCT05012436。
