Yu Dianwen, Zhang Rui, Zhou Jinping, Guo Pengpeng, Li Peixia, Ye Menghan, Liu Yani, Shi Shaojun
Department of Pharmacy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, PR China.
Department of Pharmacy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, PR China.
J Pharm Sci. 2025 Feb;114(2):1087-1094. doi: 10.1016/j.xphs.2024.11.020. Epub 2024 Dec 16.
Pirfenidone is an inhibitor of transforming growth factor-beta 1 (TGF-β1) and is being developed for the treatment of diabetic kidney disease (DKD). We assessed the pharmacokinetics (PK) and safety of a single dose of pirfenidone in individuals with CKD stages G2/G3a.
In this phase I bridging study, patients with CKD stages G2 or G3a, aged 18-70 years, with a body mass index of 18-26 kg/m, and glomerular filtration rate (eGFR) ranging from 45 to 89 ml/min/1.73 m, received a single oral dose of 400 mg pirfenidone capsules 30 min after a standard breakfast. The pharmacokinetic parameters of the two groups were measured and compared after blood and urine collection. The co-primary endpoints were the area under the plasma concentration-time curve from time zero to 36 h (AUC-) and the maximum observed plasma concentration (C) of pirfenidone. Safety was a secondary endpoint. The trial has been registered on ClinicalTrials.gov (ChiCTR2300077297).
A total of 20 subjects participated in this study. There were no significant differences between the control group and the patient group (CKD stages G2/G3a) in terms of plasma C, the time to reach the maximum observed concentration (T), and elimination half-life(t). However, the Vz/F of the patient group (CKD G2 stage) was significantly higher than that of the control group. Renal accumulation rate, renal clearance rate (CLr), and urine drug concentration also showed no significant differences. No severe adverse events occurred during the trial.
These results indicate that the PK and safety of pirfenidone are not influenced by renal function. Individuals with renal impairment may not require dose adjustments.
吡非尼酮是一种转化生长因子-β1（TGF-β1）抑制剂，正被开发用于治疗糖尿病肾病（DKD）。我们评估了单剂量吡非尼酮在慢性肾脏病（CKD）G2/G3a期患者中的药代动力学（PK）和安全性。
在这项I期桥接研究中，年龄在18至70岁、体重指数为18至26 kg/m²、肾小球滤过率（eGFR）为45至89 ml/min/1.73 m²的CKD G2或G3a期患者，在标准早餐后30分钟口服单剂量400 mg吡非尼酮胶囊。采集血液和尿液后，测量并比较两组的药代动力学参数。共同主要终点是从时间零点至36小时的血浆浓度-时间曲线下面积（AUC₀₋₃₆h）和吡非尼酮的最大观察血浆浓度（Cmax）。安全性是次要终点。该试验已在ClinicalTrials.gov上注册（ChiCTR2300077297）。
共有20名受试者参与本研究。对照组与患者组（CKD G2/G3a期）在血浆Cmax、达到最大观察浓度的时间（Tmax）和消除半衰期（t1/2）方面无显著差异。然而，患者组（CKD G2期）的Vz/F显著高于对照组。肾脏蓄积率、肾脏清除率（CLr）和尿药浓度也无显著差异。试验期间未发生严重不良事件。
这些结果表明，吡非尼酮的PK和安全性不受肾功能影响。肾功能受损的个体可能无需调整剂量。
