Estudios "in vitro" e "in vivo" de la absorción percutánea de la bemiparinaMétodos de valoración.

Résumé

For a decade, the pharmacologic treatment of deep vein thrombosis (DVT) consists in the administration of low molecular weight heparin (LMWH) (3-9 kD). Transdermal administration of xenobiotics has some advantages in comparison to the conventional routes, althought this route isn¿t generalizable for all xenobiotics. We have select the BEMIPARIN (3.6 kD) out of all LMWH, because at the beginning, we thik the study can get useful results for the prevention of thromboembolic disease, with all advantages that the new administration way could contribute at this therapeutic field. The objectives of this study are: - Determination of the capacity of Bemipain¿s cutaneous penetration in vitro e in vivo. - Analyzation of the samples by the method of the King Spanish Pharmacopeia, 2002, and search of two alternating methods. For the in vitro trials, we employ human skin as biologic membrane. The experiments carry out in standarizaded diffusion cells. These cells have two compartiments, donor and receptor. For the in vivo trials, the animal employed is Wistar male rat (250-300 g of weight). We apply on the back zone a cape of 1 mm of thickness, of the formulation selected in the in vitro trials. Previous the day of experiment, we implant a cannula of silicone in the jugular vein for the taking of blood samples. The samples are analyzated by the determination of anti-Xa activity (method of King Spanish Pharmacopeia, 2002), and as alternative we study the possibility of employ two methods of high performance liquid chromatography (HPLC): 1. Determination of sodic Bemiparin by ultraviolet deteccion. 2. Determination of sodic Bemiparin by fluorescence, through of dissaccharide produced by an enzymatic digestion.