Partially competitive inhibition of intestinal baclofen absorption by beta-alanine, a nonessential dietary aminoacid.
In situ intestinal absorption of baclofen in the rat in the presence of beta-alanine has been investigated. Through the perfusion of 0.50 mM baclofen solutions containing variable concentrations of the aminoacid (from 5 to 100 mM), a partially competitive inhibition of baclofen absorption was characterized: absorption rate pseudoconstants of the spasmolytic drug decrease as beta-alanine concentration increases, until a limiting value is obtained (36.8 per cent of that found for baclofen alone). A computer method was developed in order to calculate parameters governing baclofen absorption in the presence of beta-aminoacid, with the following results: Vm = 11.22 mM h-1; Km = 7.42 mM; Ki = 2.45 mM; alpha = 2.78; r = 0.998. Kinetic absorption parameters for beta-alanine in the presence of 0.50 mM baclofen were also assessed: Vm = 49.88 mM h-1; Km = 12.16 mM; r = 0.998, which, as can be expected, do not significantly differ from those previously found in the absence of the spasmolytic. It is concluded that baclofen and beta-alanine compete for the same intestinal carrier system, although the values of the interaction parameters, particularly Ki, can be more or less biased due to the limitations of the procedure and/or to the existence of some other carrier system for absorption. Possible practical implications of this phenomenon are briefly discussed.
Polache
A
A
Department of Pharmaceutics, University of Valencia, Spain.
Plá-Delfina
J M
JM
Merino
M
M
D000818:Animals; D001418:Baclofen / Q000493:pharmacokinetics*; D004347:Drug Interactions; D007408:Intestinal Absorption / Q000187:drug effects*; D007421:Intestine, Small / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D014867:Water / Q000378:metabolism; D015091:beta-Alanine / Q000493:pharmacokinetics / Q000494:pharmacology*
D014867:Water; D015091:beta-Alanine; D001418:Baclofen