Pharmacokinetic properties of a new sustained-release pregabalin tablet in subjects with reduced renal function

Maria Park; Suein Choi; Sungpil Han; Wonsuk Shin; Anhye Kim; Seunghoon Han; Bomin Kim; Yeji Lim; Hyounggyoon Yoo

doi:10.12793/tcp.2023.31.e20

Pharmacokinetic properties of a new sustained-release pregabalin tablet in subjects with reduced renal function

Transl Clin Pharmacol. 2023 Dec;31(4):226-237. doi: 10.12793/tcp.2023.31.e20. Epub 2023 Dec 20.

Authors

Maria Park^{1

2}, Suein Choi^{1

2}, Sungpil Han^{1

2}, Wonsuk Shin^{3

4}, Anhye Kim^{3

4}, Seunghoon Han^{1

2}, Bomin Kim⁵, Yeji Lim⁵, Hyounggyoon Yoo^{3

4}

Affiliations

¹ Department of Clinical Pharmacology and Therapeutics, The Catholic University of Korea Seoul St. Mary's Hospital, Seoul 06591, Korea.
² Department of Pharmacology, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea.
³ Department of Clinical Pharmacology and Therapeutics, CHA Bundang Medical Center, Seongnam 13520, Korea.
⁴ Department of Clinical Pharmacology and Therapeutics, CHA University School of Medicine, Seongnam 13520, Korea.
⁵ Clinical Development and Medical Division, Yuhan Corporation, Seoul 06927, Korea.

Abstract

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/1.73m² (Cohort A) and 30-60 mL/min/1.73m² (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_max), and area under the concentration-time profile from 0 to the last measurable time (AUC_last) 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_max, and AUC_last 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 m² were within the range of steady-state concentrations simulated after once-daily Y150T dosing in subjects with eGFR 90 mL/min/1.73 m². 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.

Trial registration: ClinicalTrials.gov Identifier: NCT05012436.

Keywords: Delayed-Action Preparations; Pharmacokinetics; Pregabalin; Renal Insufficiency.

Associated data

ClinicalTrials.gov/NCT05012436