Siriraj Medical Journal (May 2016)
Comparative Fasting Bioavailability of 2 Different Betahistine Dihydrochloride 24-mg Tablets: A Single- Dose, Randomized-Sequence, Open-Label, 2-Period Crossover Study in Healthy Thai Volunteers
Abstract
Objective: To evaluate the bioequivalence of 24 mg betahistine dihydrochloride tablets between the test product (Stei® ) and the reference product (Serc® ) in healthy Thai volunteers. Methods: This was an open-label, randomized sequence, single-dose, two-period crossover study in 24 healthy volunteers. Half of the volunteers received a single dose of test product 24 mg and then reference product 24 mg after a minimum 7-day washout period. The remaining half of volunteers received the reference product first and then the test product with the same washout period. Blood samples were obtained at pre-dose and over 14 hours after dosing. Plasma concentrations of 2-pyridylacetic acid (2-PAA), a major metabolite of betahistine were quantified by using liquid chromatography with tandem mass spectrometry (LC-MS/MS). Tolerability in volunteers were assessed during the study. Results: Statistical comparison of the main pharmacokinetic parameters showed no significant difference between test and reference. The geometric mean ratios of 2-PAA between the test and reference products were 96.44%, 96.99%, and 94.56% for Cmax, AUC0-t, and AUC0-∞, respectively. These pharmacokinetic parameter values lie within the FDA and European Medicines Agency specified bioequivalence limit (80-125%). No serious adverse events related to the studied drugs were found. Conclusion: It can be concluded that these two betahistine dihydrochloride products were considered bioequivalent.
