The Effect of Food on the Bioavailability of Ebastine

Two studies were performed to characterize the influence of food on the bioavailability of the current formulation of ebastine tablets. Study 1 was an open label, randomized, three-period, crossover food effect study where 18 healthy male volunteers received 10 mg ebastine after an overnight fast, a low-fat breakfast, and a high-fat breakfast. Study 2 was an open label, randomized, two period crossover food effect study where 12 healthy male volunteers received 20 mg ebastine after both an overnight fast and a high-fat breakfast. Plasma samples were obtained at selected times and analyzed for ebastine and carebastine, the active metabolite of ebastine, using a validated high-performance liquid chromatography assay. Biopharmaceutic parameters for carebastine, area under the plasma concentration-time curves (AUC (0-infinity)), and maximum plasma concentrations (C ( max ) ), were estimated using noncompartmental techniques and analyzed for statistical differences. AUC (0-infinity) and C(max estimates were 40%-50% and 30%-40% higher under fed conditions as compared with fasting conditions. The time to reach maximum concentrations (T(max)), the terminal elimination rate (K(e) ), and the half-life (t(1/2) ) were not significantly altered by the ingestion of a low-fat or high-fat meal. Statistical analyses of the natural logarithmic transformed data for AUC ((0-infinity) and C(max) also demonstrated significant differences between fasted and fed (low-fat and high-fat) conditions. This indicates that food had a statistically significant effect on the rate and extent of carebastine formation. Therefore, it may be concluded that administration with food maximizes the bioavailability of carebastine.