Pharmacokinetics and safety of pirfenidone in individuals with chronic kidney disease (CKD) stage G2 and G3a: a single-dose, Phase I, Bridging study

Dianwen Yu; Rui Zhang; Jinping Zhou; Pengpeng Guo; Peixia Li; Menghan Ye; Yani Liu; Shaojun Shi

doi:10.1016/j.xphs.2024.11.020

Pharmacokinetics and safety of pirfenidone in individuals with chronic kidney disease (CKD) stage G2 and G3a: a single-dose, Phase I, Bridging study

J Pharm Sci. 2024 Dec 16:S0022-3549(24)00546-X. doi: 10.1016/j.xphs.2024.11.020. Online ahead of print.

Authors

Dianwen Yu¹, Rui Zhang¹, Jinping Zhou¹, Pengpeng Guo¹, Peixia Li¹, Menghan Ye¹, Yani Liu², Shaojun Shi³

Affiliations

¹ Department of Pharmacy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, P.R. China.
² Department of Pharmacy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, P.R. China. Electronic address: yani_liu@hotmail.com.
³ Department of Pharmacy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, P.R. China. Electronic address: sjshicn@163.com.

PMID: 39694267
DOI: 10.1016/j.xphs.2024.11.020

Abstract

Background and objective: 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.

Methods: 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/m², and glomerular filtration rate (eGFR) ranging from 45 to 89 ml/min/1.73m², received a single oral dose of 400 mg pirfenidone capsules 30 minutes 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 hours (AUC₀-₃₆) and the maximum observed plasma concentration (C_max) of pirfenidone. Safety was a secondary endpoint. The trial has been registered on ClinicalTrials.gov (ChiCTR2300077297).

Results: 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_max, the time to reach the maximum observed concentration (T_max), and elimination half-life(t_1/2). 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.

Conclusions: 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.

Keywords: DN; PK; Phase I; Pirfenidone; single-dose.