ABSTRACT
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.
ABSTRACT
BACKGROUND: The current study was conducted to find out whether two oral preparations of 300 mg gabapentin (the test and reference capsules) were bioequivalent. SUBJECTS AND METHODS: This was a randomized, single-blind, crossover study under fasting condition, with a 7-day washout period, which included 37 healthy adult male and female subjects. After an overnight fast, subjects were given, orally, one capsule of the test drug or of the reference drug. Blood samples were drawn immediately before taking the drug, then at 20 and 40 minutes, and 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 15, and 24 hours after dosing, to evaluate pharmacokinetic parameters of the single dose administration, ie, the area under the plasma concentration-time curve (AUC) from time zero to 24 hours (AUCt), AUC from time zero to infinity (AUC(inf)), the peak plasma concentration of the drug (Cmax), time needed to achieve Cmax (tmax), and the elimination half-life (t1/2). The plasma concentrations of gabapentin were determined using validated high-performance liquid chromatography with ultraviolet detection. RESULTS: The geometric mean ratios (90% confidence interval) of the test drug/reference drug for gabapentin were 103.15% (90.38%-117.72%) for AUCt, 103.53% (90.78%-118.07%) for AUC(inf), and 108.06% (96.32%-121.24%) for Cmax. The differences in tmax and t1/2 values between the test and reference drug products for gabapentin were not statistically significant. Light-headedness, nausea, and headache were encountered during the study, but they were all mild and well tolerated. The 90% confidence intervals of the test/reference AUC ratio and Cmax ratio of gabapentin were within the acceptance range for bioequivalence. CONCLUSION: The two preparations of gabapentin 300 mg capsule were bioequivalent, thus both can be used interchangeably in the clinical setting.
