Bioequivalence of two formulations of pregabalin 150-mg capsules under fasting conditions in healthy male subjects
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Background: Pregabalin binds to the α2δ auxiliary subunit of voltage-gated calcium channels, which are widely distributed throughout the central and peripheral nervous systems and modulate calcium-dependent neurotransmitter release. Pregabalin is indicated for the treatment of peripheral and central neuropathic pain, partial seizures with or without secondary generalization, and treatment of generalized anxiety disorder (GAD).
Objective: The purpose of this study was to assess the bioequivalence of two different formulations of pregabalin 150-mg capsules in healthy Korean male subjects under fasting conditions.
Methods: This bioequivalence study was based on an open-label, single-dose, randomized, 2-period, 2-sequence crossover design with a washout period of 7 days. Blood samples for pharmacokinetic (PK) evaluation were collected up to 24 hours postdose. Plasma concentrations of pregabalin were determined using a validated LC-MS/MS method. PK parameters were determined using noncompartmental analysis. Bioequivalence was assumed if the 90% confidence intervals (CIs) for the test/reference ratios of log-transformed C _max and AUC _last values met the bioequivalence criteria specified by Korean regulatory guidelines (90% CI 0.8 - 1.25).
Results: The extent of exposure in terms of AUC _last amounted to 26,018.3 - 3,580.8 µg×h/L for the test formulation and 25,680.2 ± 3,083.6 µg×h/L for the reference formulation. C _max reached values of 4,782.7 ± 1,124.2 µg/L and 4,654.0 ± 911.4 µg/L for the test product and reference product, respectively. The geometric mean ratio and 90% CIs of the test product to the reference product were 1.0132 (0.9862 - 1.0351) for AUC _last and 1.0153 (0.9351 - 1.1044) for C _max , which were well within the range necessary to establish bioequivalence (90% CI 0.8 - 1.25).
Conclusions: The bioequivalence between test and reference formulations under fasting conditions was confirmed both in terms of the rate and extent of absorption.
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