Evaluation of the membrane permeability (PAMPA and skin) of benzimidazoles with potential cannabinoid activity and their relation with the Biopharmaceutics Classification System (BCS).

Autor: Alvarez-Figueroa MJ; Departamento de Farmacia, Facultad de Química, Pontificia Universidad Católica de Chile, Vicuña Mackenna, Santiago, Chile. mjalvare@uc.cl, Pessoa-Mahana CD, Palavecino-González ME, Mella-Raipán J, Espinosa-Bustos C, Lagos-Muñoz ME
Jazyk: angličtina
Zdroj: AAPS PharmSciTech [AAPS PharmSciTech] 2011 Jun; Vol. 12 (2), pp. 573-8. Date of Electronic Publication: 2011 May 04.
DOI: 10.1208/s12249-011-9622-1
Abstrakt: 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).
Databáze: MEDLINE
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