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 (AUC0-t), area under the plasma concentration-time curve from time zero to infinity (AUC0-∞), maximum plasma concentration (Cmax), time to maximum plasma concentration (tmax), and terminal half-life (t1/2). The 90% confidence intervals (CIs) for the geometric mean ratios of test formulation/reference formulation were calculated for the AUC and Cmax parameters; while tmax difference was analyzed nonparametrically on the original data using the Wilcoxon matched-pairs test, and t1/2 difference was analyzed using Student's paired t-test. RESULTS The mean (standard deviation [SD]) AUC0-t, AUC0-∞, Cmax, and t1/2 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) AUC0-t, AUC0-∞,Cmax, and t1/2 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) tmax 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 AUC0-t, 101.35% (98.66%-104.11%) for AUC0-∞, and 104.19% (98.75%-109.93%) for Cmax. CONCLUSION The study concluded that the two formulations of pregabalin capsules studied were bioequivalent.