Pharmacokinetic equivalence study of two formulations of the anticonvulsant pregabalin

Abstract

PurposeThe 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.MethodsThis 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.ResultsThe 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.ConclusionThe study concluded that the two formulations of pregabalin capsules studied were bioequivalent.

A Comparative Pharmacokinetics Study of the Anti-Parkinsonian Drug Pramipexole

“…With this concept, drug regulators require that generic formulations should have equivalent clinical effects with its innovator counterparts, resulting in interchangeability of both products. In compliance with the requirement, we have also conducted bioequivalence studies on several generic formulations [21,22,23,24]. Our current study on pramipexole was carried out with the same requirements in mind.…”

Alleviation of pain in painful diabetic neuropathy

“…The pharmacokinetic parameters of an orally administered single dose of a PREG capsule of 150 mg revealed that C max was 3.99 ng/L, AUC was 28.31 ng/mL x h, T max was 1.00 h and T 1/2 was 5.66 h [87] . The kinetics of PREG showed linear features (proportional to the dosage up to 900 mg per day) [88] .…”

Determining the Toxicological Significance of Pregabalin in Fatalities

“…The average fatal dose of pregabalin was found to be different centrally (54.1 mg/L) and peripherally (45.3, and 206.7 mg/L). Even in some non-fatal pregabalin overdose cases the serum concentration of this drug was found to be varied depending upon the condition of the person such as 20.8 mg/L was found when a person is drowsy but with no toxic symptoms founds, 60 mg/L was found after 24 hours of the pregabalin ingestion and 66.5 mg/L was found at the time of coma [16][17][18][19][20].…”