Puesta a punto de la técnica de Ussing Chamber para estudios de permeabilidad intestinal en tejido de cerdo / Optimization of the Ussing Chamber Technique for studies of intestinal permeability in pig tissue

El Sistema de Clasificación Biofarmacéutica es un marco científico para clasificar ingredientes farmacéuticos activos en base a su solubilidad acuosa y su permeabilidad intestinal, que cuando se combina con la disolución del producto toma en cuenta los tres factores principales que gobiernan la velocidad y el alcance de la absorción de un fármaco a partir de formas posológicas orales sólidas de liberación inmediata. Cuando los fármacos cumplen con determinados criterios biofarmacéuticos este sistema permite reemplazar los estudios in vivo de biodisponibilidad / bioequivalencia por estudios in vitro. La permeabilidad intestinal de los IFAs puede ser estudiada por diferentes métodos, uno de ellos es la técnica de Ussing Chamber que utiliza una porción de tejido intestinal. La ventaja de esta técnica es que permite conservar las capacidades funcionales de los tejidos. En la puesta a punto de esta nueva técnica se obtuvieron datos concordantes con bibliografía. Se evaluó la permeabilidad de ibuprofeno, metoprolol y atenolol (drogas de alta y baja permeabilidad) utilizando Ussing Chamber con intestino delgado de cerdo. Contar con esta técnica en el Departamento de Farmacología representa un valioso complemento a las metodologías ya utilizadas: estudios in vitro (células Caco-2 y MDCK) e in situ (perfusión intestinal en rata).

The Biopharmaceutical Classification System is a scientific framework for classifying Active Pharmaceutical Ingredients based on their aqueous solubility and their intestinal permeability which, when combined with the dissolution of the product takes into account the three main factors that govern the absorption speed and extent of a drug from immediate-release solid oral dosage form. When drugs meet certain biopharmaceutical criteria, this system allows in vivo bioavailability / bioequivalence studies to be replaced by in vitro studies. The intestinal permeability of APIs can be studied by different methods, one of them is the Ussing Chamber technique that uses a portion of intestinal tissue. The advantage of this technique is that it allows to conserve the functional capacities of tissues. In the development of this new technique, concordant data with bibliography was obtained. The permeability of ibuprofen, metoprolol and atenolol (high and low permeability drugs) was evaluated utilizing the Ussing Chamber Technique with pig small intestine. To have this technique in the Department of Pharmacology represents a valuable complement to the methodologies already used; both in vitro (Caco-2 and MDCK cells) and in situ (intestinal perfusion in rat) studies.

Computer-Aided Recognition of ABC Transporters Substrates and Its Application to the Development of New Drugs for Refractory Epilepsy.

Despite the introduction of more than 15 third generation antiepileptic drugs to the market from 1990 to the moment, about one third of the epileptic patients still suffer from refractory to intractable epilepsy. Several hypotheses seek to explain the failure of drug treatments to control epilepsy symptoms in such patients. The most studied one proposes that drug resistance might be related with regional overactivity of efflux transporters from the ATP-Binding Cassette (ABC) superfamily at the blood-brain barrier and/or the epileptic foci in the brain. Different strategies have been conceived to address the transporter hypothesis, among them inhibiting or down-regulating the efflux transporters or bypassing them through a diversity of artifices. Here, we review scientific evidence supporting the transporter hypothesis along with its limitations, as well as computer-assisted early recognition of ABC transporter substrates as an interesting strategy to develop novel antiepileptic drugs capable of treating refractory epilepsy linked to ABC transporters overactivity.