title: Evaluation of the membrane permeability (PAMPA and skin) of benzimidazoles with potential cannabinoid activity and their relation with the Biopharmaceutics Classification System (BCS).
abstract: The permeability of five benzimidazole derivates with potential cannabinoid activity was determined in two models of membranes, parallel artificial membrane permeability assay (PAMPA) and skin, in order to study the relationship of the physicochemical properties of the molecules and characteristics of the membranes with the permeability defined by the Biopharmaceutics Classification System. It was established that the PAMPA intestinal absorption method is a good predictor for classifying these molecules as very permeable, independent of their thermodynamic solubility, if and only if these have a Log P(oct) value <3.0. In contrast, transdermal permeability is conditioned on the solubility of the molecule so that it can only serve as a model for classifying the permeability of molecules that possess high solubility (class I: high solubility, high permeability; class III: high solubility, low permeability).
authors.affiliation: Departamento de Farmacia, Facultad de Química, Pontificia Universidad Católica de Chile, Vicuña Mackenna, Santiago, Chile. mjalvare@uc.cl
authors.forename: M Javiera
authors.initials: MJ
authors.lastname: Alvarez-Figueroa
authors.forename: C David
authors.initials: CD
authors.lastname: Pessoa-Mahana
authors.forename: M Elisa
authors.initials: ME
authors.lastname: Palavecino-González
authors.forename: Jaime
authors.initials: J
authors.lastname: Mella-Raipán
authors.forename: Cristián
authors.initials: C
authors.lastname: Espinosa-Bustos
authors.forename: Manuel E
authors.initials: ME
authors.lastname: Lagos-Muñoz
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001562:Benzimidazoles / Q000145:classification / Q000493:pharmacokinetics* / Q000592:standards; D001702:Biopharmaceutics / Q000379:methods* / Q000592:standards; D002186:Cannabinoids / Q000145:classification / Q000493:pharmacokinetics* / Q000592:standards; D002463:Cell Membrane Permeability / Q000187:drug effects / Q000502:physiology*; D004353:Drug Evaluation, Preclinical / Q000379:methods / Q000592:standards; D007408:Intestinal Absorption / Q000187:drug effects / Q000502:physiology; D008567:Membranes, Artificial; D011237:Predictive Value of Tests; D012869:Skin Absorption / Q000187:drug effects / Q000502:physiology*; D013552:Swine
chemical_list: D001562:Benzimidazoles; D002186:Cannabinoids; D008567:Membranes, Artificial