Estudio del mecanismo de absorci¿®n intestinal del acamprosato en la rata.

Abstract

Acamprosate was approved in different countries of the European Union and recently, the FDA has approved in the USA and is indicated for the maintenance of abstinence from alcohol in patients with alcohol dependence who are abstinent at treatment initiation as a part of a comprehensive management program that includes psychosocial support. One of the main problems of this drug is its low bioavailability in human (around 10%) when it is administered as enteric coated tablet. At the moment of the preparation of this thesis, and despite the great amount of studies done, relevant aspects of its pharmacokinetics properties as the intestinal routes of absorption were unknown. With the purpose of identified the reason of its poor oral bioavailability, the main aim of this study was to caracterize the intestinal absorption mechanism of acamprosato in the rat jejunum, using an in vitro technique. Other objectives was to study the influence of different factors, as alcoholism, diet or the present of some structurally related compounds in the intestinal lumen, in the intestinal absorption of acamprosato. Intestinal acamprosate absorption was found to occur mainly by passive diffusion in the rat mid-jejunum in the wide concentration of acamprosato used. And this diffusion of the drug could take place by the transcelular route (across the intestinal membrane) or by the paracellular using the tight junction. Moreover, neither chronic ethanol intake nor the type of diet (liquid vs. solid) seems to alter the intestinal absorption of the drug, so in this type of experiment it is possible to use animals fed a solid diet. The results of the inhibition studies with structurally related aminoacids (GABA, taurine, proline, and glycine) suggest that acamprosate in the rat jejunum, could be transported, in part, by a carrier system. However, its repercussion in the overall process would be not quantitative important.