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 of Two Oral Tablet Formulations of Betahistine 24 Mg: Single-Dose, Open-Label, Randomized, Two-Period Crossover Comparison in Healthy Individuals

Larisa Estrada- Marín, Beatriz Cedillo- Carvallo, Augusto Herrera- Coca, Gabriela Bravo- Barragán, Olga Guzmán García and Alejandro Ruiz- Argüelles

A bioequivalence study of betahisitine tablets was conducted. Thirty two healthy Mexican mestizo volunteers received each test (T) and reference (R) formulations of betahistine at a dose of 24 mg in a 2 × 2 cross-over study. There was a three-day washout period between the two formulations. Plasma concentrations of betahistine were monitored by an ultra-performance liquid chromatography coupled to tandem mass spectrometry (UPLC/MS/MS) for over a period of 24 h after the administration. AUC0-t (the area under the plasma concentration–time curve from time 0 to last sampling time) and AUC 0-∞ (that from time 0 to infinity) were calculated by the linear-log trapezoidal rule method. Cmax (maximum plasma drug concentration) and Tmax (time to reach Cmax) were compiled from the plasma concentration–time data. Analysis of variance was carried out using logarithmically transformed AUC and Cmax, and untransformed Tmax. The mean of AUC0-t was 7139.8 ng mL−1 h−1 (test medication) and 6714.4 ng mL−1 h−1 (reference medication) and that of AUC0-∞ were 7660.2 (test) and 6850.3 ng mL-1 h-1 (reference). Cmax values of 1716.2 and 1677.3 ng mL−1 were achieved for the test and the reference medication, respectively. Tmax were determined at 0.86 h for the test and 0.87 h for the reference formulations. The 90% confidence intervals for AUC0-t, AUC0-∞ and Cmax were 0.994-1.102, 0.994-1.131 and 0.969-1.069, respectively, satisfying the bioequivalence criteria of the Mexican Comisión Federal Para la Protección Contra Riesgos Sanitarios, the European Committee for Proprietary Medicinal Products and the US Food and Drug Administration Guidelines. These results indicate that the two medications of betahistine are bioequivalent and, thus, may be prescribed interchangeably.