title: The effect of food on the bioavailability of ebastine.
abstract: 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.
authors.affiliation: Rhône-Poulenc Rorer Research and Development, Collegeville, PA 19426, USA.
authors.forename: H S
authors.initials: HS
authors.lastname: Pentikis
authors.forename: M Y
authors.initials: MY
authors.lastname: Huang
authors.forename: M B
authors.initials: MB
authors.lastname: Dorr
authors.forename: D L
authors.initials: DL
authors.lastname: Heald
mesh_terms: D000328:Adult; D019540:Area Under Curve; D001682:Biological Availability; D002090:Butyrophenones / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D018592:Cross-Over Studies; D004041:Dietary Fats / Q000494:pharmacology; D018565:Food-Drug Interactions; D006207:Half-Life; D006634:Histamine H1 Antagonists / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010880:Piperidines / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D013607:Tablets
chemical_list: D002090:Butyrophenones; D004041:Dietary Fats; D006634:Histamine H1 Antagonists; D010880:Piperidines; D013607:Tablets; C058249:ebastine