Evidence of competitive inhibition for the intestinal absorption of baclofen by phenylalanine

• Published in: International journal of pharmaceutics Vol. 132; no. 1; pp. 63 - 69
• Main Authors: Cejudo-Ferragud, E., Nácher, A., Polache, A., Cercós-Fortea, T., Merino, M., Casabó, V.G.
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 30.04.1996; Elsevier
• Subjects: Baclofen; Biological and medical sciences; Competitive inhibition; Intestinal absorption; Medical sciences; Michaelis-Menten kinetics; Muscle; Pharmacology. Drug treatments; Phenylalanine; γ-Aminobutyric acid; Michaelis-Menten kinetics; γ-Aminobutyric acid; Phenylalanine; Intestinal absorption; Competitive inhibition; Baclofen; Rat; Digestive system; Muscle relaxant; Interaction; Biological transport; Rodentia; Gut; Vertebrata; Mammalia; Absorption; Antispasmodic agent; Aminoacid; Animal; Aromatic compound; Pharmacokinetics
• ISSN: 0378-5173; 1873-3476
• DOI: 10.1016/0378-5173(95)04342-X

Previous studies showed that the absorption of the antispastic drug baclofen, in the rat middle intestine, is inhibited by β-alanine, γ-aminobutyric acid (GABA) and leucine. It was concluded that baclofen intestinal transport was mediated, at least in part, by the β-, γ- and α-amino acid carriers. We therefore focused our next studies on the analysis of the possible inhibition of drug absorption by an aromatic α-amino acid model compound, phenylalanine. An in situ study in the rat small intestine was undertaken in order to evaluate the effect of phenylalanine on baclofen absorption and to establish the inhibition model. Assays using isotonic perfusion solutions of 0.5 mM baclofen with initial phenylalanine concentrations ranging from 0 to 100 mM are reported. The results show that the absorption rate pseudoconstants of the drug decrease as the phenylalanine concentration increases, with a limiting value of 0.33 h −1 ( ±0.06). Complete competitive inhibition in the presence of a second component could define the interaction phenomena between these substances, since higher concentrations of phenylalanine do not completely abolish baclofen absorption. We have completed the studies using phenylalanine and GABA together as inhibitors of drug absorption. An isotonic perfusion solution of 0.5 mM baclofen in the presence of 100 mM phenylalanine and 100 mM GABA was perfused. Under these conditions the absorption rate pseudoconstant of baclofen decreases until 0.16 h −1 (±0.06).