Pharmacokinetics of a New, Once-Daily, Sustained-release Pregabalin Tablet in Healthy Male Volunteers

Purpose: A new sustained-release (SR) pregabalin formulation (YHD1119) designed for once-daily dosing has recently been developed to improve patient adherence. This study aimed to compare the pharmacokinetics of pregabalin SR and immediate-release (IR) formulations after multiple oral doses and to assess the effect of food on the pharmacokinetic profile of the pregabalin SR formulation after a single dose in healthy individuals. Methods: Two clinical trials were conducted: a randomized, open-label, multiple-dose, 2-treatment, 2-period crossover study to evaluate the steady-state pharmacokinetic properties of SR treatment (pregabalin SR 300 mg once daily for 3 days) and IR treatment (pregabalin IR 150 mg twice daily for 3 days) under fed conditions and a randomized, open-label, single-dose, 2-treatment, 2-period, crossover study to evaluate the effect of food intake on the pharmacokinetic properties of the pregabalin SR formulation. Plasma concentrations of pregabalin were measured using LC-MS/MS. The AUC and C_max for pregabalin were calculated using noncompartmental method and compared between treatments in each study. Findings: Thirty-one individuals in the bioequivalence study and 23 in the food effect study completed the pharmacokinetic sampling. The geometric mean ratios of C_max,ss and AUC_0–τ between the SR and IR formulations were 1.1642 (90% CI, 1.1043–1.2272) and 0.9704 (90% CI, 0.9372–1.0047), respectively. The geometric mean ratios of C_max and AUC_0–last between the SR formulation in the fed state and in the fasted state were 1.6514 (90% CI, 1.3820-1.9732) and 1.7899 (90%CI, 1.4499-2.2097), respectively. Implications: The bioavailability of the pregabalin SR 300 mg formulation is increased if taken with a high-fat meal. Once-daily pregabalin SR 300 mg is bioequivalent to twice-daily pregabalin IR 150 mg under fed conditions at steady state. The pregabalin SR formulation is expected to improve patient adherence. ClinicalTrials.gov identifiers: NCT02783183 (bioequivalence study) and NCT03191136 (food effect study).