Pharmacokinetic equivalence study of two formulations of the anticonvulsant pregabalin

PURPOSE: The present study was conducted to evaluate whether the bioavailability of pregabalin capsules 150 mg manufactured by PT Dexa Medica was equivalent to the reference formulation. METHODS: This was a randomized, open-label, two-period, two-sequence, and crossover study under fasting condition, with a 1-week washout period. Plasma concentrations of pregabalin from 20 subjects were determined by using a validated liquid chromatography with tandem mass spectrometry (LC-MS/MS) detection method. Pharmacokinetic parameters assessed in this study were: area under the plasma concentration–time curve from time zero to last observed quantifiable concentration (AUC(0–t)), area under the plasma concentration–time curve from time zero to infinity (AUC(0–∞)), maximum plasma concentration (C(max)), time to maximum plasma concentration (t(max)), and terminal half-life (t(1/2)). The 90% confidence intervals (CIs) for the geometric mean ratios of test formulation/reference formulation were calculated for the AUC and C(max) parameters; while t(max) difference was analyzed nonparametrically on the original data using the Wilcoxon matched-pairs test, and t(1/2) difference was analyzed using Student’s paired t-test. RESULTS: The mean (standard deviation [SD]) AUC(0–t), AUC(0–∞), C(max), and t(1/2) of pregabalin from the test formulation were 27,845.86 (4,508.27) ng · h/mL, 28,311.70 (4,790.55) ng · h/mL, 3,999.71 (801.52) ng/mL, and 5.66 (1.20) hours, respectively; while the mean (SD) AUC(0–t), AUC(0–∞),C(max), and t(1/2) of pregabalin from the reference formulation were 27,398.12 (4,266.28) ng · h/mL, 27,904.24 (4,507.31) ng · h/mL, 3,849.50 (814.50) ng/mL, and 5.87 (1.25) hours, respectively. The median (range) t(max) of pregabalin from the test formulation and reference formulation was 1.00 (0.67–2.00) hours and 1.00 (0.67–3.00) hours, respectively. The 90% CIs for the geometric mean ratios of test formulation/reference formulation for pregabalin were 101.54% (98.75%–104.41%) for AUC(0–t), 101.35% (98.66%–104.11%) for AUC(0–∞), and 104.19% (98.75%–109.93%) for C(max). CONCLUSION: The study concluded that the two formulations of pregabalin capsules studied were bioequivalent.