INFLUENCE OF LEUCINE ON INTESTINAL BACLOFEN ABSORPTION AS A MODEL-COMPOUND OF NEUTRAL ALPHA-AMINO-ACIDS

The inhibitory effect of the essential a-aminoacid L-leucine on the intestinal absorption of the antispastic drug baclofen was examined by means of an in situ rat gut perfusion technique. When 0.5 mM baclofen solutions were perfused in the presence of increasing concentrations of the aminoacid (5-100 mM), the apparent absorption rate constant of the drug decreased as the initial leucine concentration increased. Higher leucine concentrations, however, did not completely abolish the absorption of the drug (at 100 mM of leucine, only 76% inhibition was observed). The interaction can be mathematically described as a complete competitive inhibition with a second component, K = 0.35 (+/- 0.08)h(-1), K-i = 0.25 (+/- 0.09)mM, AIC = -97.02. In the light of some of the absorption features of the drug, however, the residual absorption of baclofen in the presence of high leucine concentrations should be attributed to another transport system not used by leucine. Apparent parameters characterizing absorption of leucine in the presence of baclofen (0.5 mM) were V-m = 61.02 (+/- 5.46) mM h(-1); K-m = 8.04 (+/- 0.89) mM, and AIC = - 62.25. The results indicate that baclofen and leucine share some carriers in the intestinal absorption processes. Since leucine is an essential dietary aminoacid, and therefore a normal food component, this finding could be relevant in preventing interactions that would lead to a reduced oral bioavailability during baclofen therapy.