Biopharmaceutics Permeability Classification of Lorcaserin, a Selective 5‑Hydroxytryptamine 2C Agonist: Method Suitability and Permeability Class Membership

The objectives of the study were (1) to demonstrate that a Caco-2 cell-based permeability assay, developed in our laboratory, is suitable to identify the permeability classification according to the US Food and Drug Administration Biopharmaceutics Classification System guidance, and (2) to use the validated Caco-2 method to determine permeability class membership of lorcaserin. Lorcaserin, marketed in United States as Belviq, is a selective human 5-hydroxytryptamine 2C agonist used for weight management. First, the permeability of twenty commercially available drugs was determined in the apical-to-basolateral direction at a final concentration of 10 μM, with the pH of transporter buffer in the apical and basolateral compartments being 6.8 and 7.4, respectively. A rank-order relationship between in vitro permeability results and the extent of human intestinal absorption for the drugs tested was observed. Second, the apparent permeability coefficient values of lorcaserin at 2, 20, and 200 μM and apical pH values of 6.8 and 7.4 in the apical-to-basolateral direction were determined using the validated method and found to be comparable to those of the high-permeability internal standard metoprolol. Lorcaserin permeability across Caco-2 cell monolayers was not dependent on the variation of apical pH. Furthermore, lorcaserin was not a substrate for efflux transporters such as P-glycoprotein. In conclusion, using the validated Caco-2 permeability assay, it was shown that lorcaserin is a highly permeable compound.