生物学的同等性とバイオアベイラビリティのジャーナル

概要

Bioequivalence Study of Two Linezolid 600 mg Immediate-release Oral Tab-lets in a Healthy Mexican Population under Fasting Conditions

Gabriel Marcelín-Jiménez*, Lizet Gómez, Orlando Jacobo-Cabral, Leticia Contreras, Dany Batista

Objective: To share pharmacokinetic data and a bio-analytical method developed for the conduction of a bioequivalence trial of Linezolid 600-mg tablets in Mexican population.

Methods: Thirteen female and 13 male healthy volunteers were administered with a single oral dose of one 600-mg Linezolid tablet under fasting conditions, in a double-blinded cross-over design study, with blood sampling up to 24 h post-dose. Linezolid was measured by tandem Mass Spectrometry coupled to Ultra-Performance Liquid Chromatography (UPLC-MS/MS) with a validated method. Logarithmic ratios of maximal plasma Concentration (C_max) and Area under the Curve (AUC_0-24h) were used to establish 90% Confidence Intervals [CI] for bioequivalence.

Results: Both formulations (Zyvoxam™, Pfizer as reference product, and LINEZOLID generic formulation as test product) were safe and well tolerated. The analytical method proved to be linear with accuracy and precision within a range of 0.1-20 μg/mL; 90% CI for C_max and AUC_0-24h were [91.94–116.14] and [97.38–110.95], respectively, with a statistical power greater than 0.9. C_max was reached at approximately 1 h, and plasma elimination half-life (t_1/2) was around 3.29 h for both products.

Conclusion: Assayed products met the criteria established by the Mexican regulatory agency (COFEPRIS) to be declared bioequivalent. Apparently, Mexican population appears to be a high absorber/ fast metabolizer of Linezolid, exhibiting a shorter t_1/2 and a reduced total amount of drug absorbed, compared to other non-Latin populations previously reported.