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

• Published in: Clinical therapeutics 2021-08, Vol.43 (8), p.1381-1391.e1
• Main Authors: Moon, Seol Ju, Jeon, Ji-Young, Lim, Yeji, An, Taewon, Jang, Seong Bok, Kim, Sohee, Na, Woon-Sook, Lee, Sun Young, Kim, Min-Gul
• Format: Article
• Language: English
• Subjects: Area Under Curve; Bioavailability; Biological Availability; Calibration; Chromatography, Liquid; Clinical trials; Controlled release; Cross-Over Studies; Delayed-Action Preparations - pharmacokinetics; Diabetes; Diabetic neuropathy; Dosage; Drug delivery systems; Drug dosages; Evaluation; FDA approval; Food; food effect; Food intake; Healthy Volunteers; Hematology; Humans; Laboratories; Male; Meals; Patients; Pharmacokinetics; Pharmacology; pregabalin; Pregabalin - pharmacokinetics; Steady state; sustained release; Tablets - pharmacokinetics; Tandem Mass Spectrometry; Therapeutic Equivalency; Urinalysis
• ISSN: 0149-2918; 1879-114X
• DOI: 10.1016/j.clinthera.2021.06.010

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. 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 Cmax for pregabalin were calculated using noncompartmental method and compared between treatments in each study. Thirty-one individuals in the bioequivalence study and 23 in the food effect study completed the pharmacokinetic sampling. The geometric mean ratios of Cmax,ss and AUC0–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 Cmax and AUC0–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. 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).