Influence of gamma-aminobutyric acid on baclofen intestinal absorption

Since previous studies suggested that baclofen absorption in the rat middle intestine was inhibited by beta-alanine and therefore mediated, at least in part, by the beta-aminoacid carrier, we focused our new studies on the analysis of the possible inhibition of the drug by a gamma-aminoacid model compound, gamma-aminobutyric acid (GABA). A rat jejunum in situ study was undertaken in order to evaluate the effect of GABA on baclofen absorption and to establish the inhibition model. Assays using isotonic perfusion solutions of 0.5 mM baclofen with starting GABA concentrations ranging from 0 to 100 mM are reported. The results show that the absorption rate pseudoconstants of the drug decrease at the GABA concentration increases, with a limiting value of 0.65 h-1 (+/- 0.01). A partial competitive inhibition or complete competitive inhibition in the presence of a passive component could define the interaction phenomena between the two substances. Kinetic absorption parameters for GABA in the presence and absence of baclofen (Ki = 5.67 +/- 1.54, Km = 3.87 +/- 0.63) suggest the existence of more than one intestinal carrier system for baclofen or GABA.