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

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

• Park M
• Choi S
• Han S
• Shin W
• Kim A
• Han S
• Kim B
• Lim Y
• Yoo H

• KMID: 2552443
• DOI: http://doi.org/10.12793/tcp.2023.31.e20

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/1.73m ² (Cohort A) and 30–60 mL/min/1.73m ² (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 m ² were within the range of steady-state concentrations simulated after once-daily Y150T dosing in subjects with eGFR 90 mL/min/1.73 m ² . 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.

Keyword

Pharmacokinetics; Pregabalin; Delayed-Action Preparations; Renal Insufficiency