Bioequivalence and Safety of Bilastine 20 mg Administered in Three Eight-Hourly Dose Versus a Single Daily Dose: A Randomized Two-Treatment, Two-Period, Cross-Over Comparative Study.

BACKGROUND AND

OBJECTIVE

Antihistamines are an essential treatment option for cough and upper respiratory symptoms. Bilastine is a 2nd-generation antihistamine which is approved as a 20 mg once daily dose. The objective of the current study is to compare the oral bioavailability of bilastine administered thrice daily as a triple combination syrup of test product bilastine + dextromethorphan hydrobromide + phenylephrine hydrochloride (3.3 mg + 10 mg + 5 mg)/5 mL and a reference product of single-dose administration of 2.5 mg/mL (bilastine 2.5 mg) in healthy, adult, male human subjects under fed condition.

METHODS

This was an open-label, balanced, randomized, two-treatment, two-period, cross-over comparative bioavailability study. Patients were administered 10 mL of three 8-hourly doses of the triple combination test product and once daily dose of the reference product (syrup containing bilastine 2.5 mg). A 7-day washout period was implemented between doses. Blood samples were collected to assess the oral bioavailability of the test and reference products. Each subject received both treatments, serving as their own control, eliminating the need for a separate control group. Blood samples were collected pre-dose and at various intervals post-dose to determine plasma concentrations of bilastine using LC-MS/MS (Liquid Chromatography-Mass Spectrometry/Mass Spectrometry. Primary pharmacokinetic parameters were analyzed for bioequivalence using SAS version 9.4.

RESULTS

A total of 34 subjects out of 36 enrolled, successfully completed the study, and were analyzed. The geometric mean ratios of test versus reference product for the areas under the curve (AUC0-t and AUC0-∞ ) were 88.42% (84.15-92.91%) and 98.06% (93.63-102.69%), respectively, which are within the bioequivalence acceptance limits of 80.00-125.00%.

CONCLUSION

Our study concluded that the test product, bilastine + dextromethorphan hydrobromide + phenylephrine hydrochloride syrup (3.3 mg + 10 mg + 5 mg)/5 mL, and the reference product, bilastine solution 2.5 mg/mL, are bioequivalent with respect to the extent of absorption and were well tolerated.