Gabapentin Bioequivalence Study: Quantification by Liquid Chromatography Coupled to Mass Spectrometry

Abstract

The study was performed to compare the bioavailability of two gabapentin 400 mg capsule formulation (Gabapentin from Arrow Farmacêutica S/A as test formulation and Neurontin ® from Pfizer, Brazil, as reference formulation) in 26 volunteers of both sexes. The study was conducted open with randomized two period crossover design and a one week wash out period. Plasma samples were obtained over a 48 hour interval. The gabapentin was analyzed by LC/MS/MS, in the presence of pracetamole as internal standard. With plasma concentration vs. time curves, data obtained from this metabolite, the following pharmacokinetics parameters were obtained: AUC 0-t , AUC 0-inf and C max. Geometric mean of gabapentin/Neurontin ® 400 mg individual percent ratio was 100.58% AUC 0-t , 101.35% for AUC 0-inf and 97.76% for C max. The 90% confidence intervals were 92.00-109.95%, 93.00-110.44%, 88.41-108.10%, respectively. Since the 90% confidence intervals for C max , AUC 0-t and AUC 0-inf were within the 80-125% interval proposed by Food and Drug Administration, it was concluded that gabapentin 400 mg capsule was bioequivalent to Neurontin ® 400 mg capsule according to both the rate and extent of absorption.

Role of Pharmacokinetic Studies in Drug Discovery

“…This is done by using appropriate statistical methods for data analysis and adequate sample size [57]. In a study with a sufficient amount of data, mean values, variance, and confidence intervals of drug concentrations and pharmacokinetic parameters should be estimated using appropriate statistical methods [58][59][60]. Major variables such as drug concentrations and pharmacokinetic parameters should be analyzed based on their statistical properties of distribution, and data transformation such as logarithmic transformation should be performed whenever necessary.…”

Analysis of Pharmacokinetic & Pharmacodynamic Models in Oral and Transdermal Dosage Forms

“…Bioequivalence studies compare the systemic exposure profile of a test drug product to that of a reference drug product. Two pharmaceutical forms are said bioequivalent when, the drug being administered to the same individual, in the same experimental conditions and at the same dose, showed no significant differences in relation to bioavailability [7]. This studies are important in the development of inhaled medications and delivery devices.…”

“…Its volume of distribution is large, estimated as 50 to 60 L in healthy volunteers. The drug is not bound to human plasma proteins [7].…”