Document Detail

Interaction of taurine on baclofen intestinal absorption: a nonlinear mathematical treatment using differential equations to describe kinetic inhibition models.
MedLine Citation:
PMID:  8923334     Owner:  NLM     Status:  MEDLINE    
Previous studies showed that the in situ absorption of baclofen in rat jejunum was inhibited by beta-alanine, a nonessential amino acid, and therefore mediated, at least in part, by some beta-amino acid carrier. In this paper a similar study was undertaken using taurine, a sulfonic beta-amino acid, in order to evaluate its effect and to establish a general inhibition model. To achieve this goal, remaining concentrations of inhibitor were also measured and incorporated into the model. Previously, kinetic absorption in situ parameters for taurine in free solution were obtained: Vm = 27.73 +/- 9.99 mM h-1, K(m) = 8.06 +/- 2.82 mM, Ka (passive difussion component) = 0.40 +/- 0.28 h-1. Isotonic solutions containing 0.5 mM baclofen with starting taurine concentrations ranging from 0 to 100 mM were perfused in rat jejunum, and the remaining concentrations of both compounds were measured. The apparent rate pseudoconstant of the drug clearly decreased as the remaining taurine concentration increased. The interaction can be described as a complete competitive inhibition plus a second component, K, noninhibited, K = 0.58 (+/- 0.03) h-1, Ki = 20.62 (+/- 4.04) mM, Vmi = 28.12 (+/- 6.12) mM h-1, Kmi = 11.71 (+/- 2.53) mM, Kai = 0.47 (+/- 0.10) h-1. A residual absorption of baclofen in the presence of high taurine concentrations was observed, which should be attributed to another transport system not associated with the taurine carrier. In order to elucidate whether or not taurine and beta-alanine carriers are two separate entities that baclofen can use for absorption, further experiments using beta-alanine and taurine together as inhibitors (baclofen, 0.5 mM; beta-alanine, 50 mM, and taurine, 50 mM) were developed. Results indicated that baclofen and both amino acids share the same carrier in the intestinal absorption process. We have completed studies using leucine, taurine, and GABA together as inhibitors of drug absorption. An isotonic perfusion solution of 0.5 mM baclofen in the presence of 50 mM leucine, 25 mM taurine, and 25 mM GABA was perfused. Under these conditions the absorption rate pseudoconstant of baclofen decreases until 0.080 h-1 (+/- 0.069). Practical implications of these phenomena are briefly discussed.
M J Moll-Navarro; M Merino; V G Casabó; A Nácher; A Polache
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Journal of pharmaceutical sciences     Volume:  85     ISSN:  0022-3549     ISO Abbreviation:  J Pharm Sci     Publication Date:  1996 Nov 
Date Detail:
Created Date:  1997-02-18     Completed Date:  1997-02-18     Revised Date:  2003-11-14    
Medline Journal Info:
Nlm Unique ID:  2985195R     Medline TA:  J Pharm Sci     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  1248-54     Citation Subset:  IM    
Department of Pharmaceutics, Faculty of Pharmacy, University of Valencia, Burjassot, Spain.
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MeSH Terms
Baclofen / antagonists & inhibitors*,  pharmacology
Intestinal Absorption / drug effects*
Leucine / pharmacology
Models, Chemical
Muscle Relaxants, Central / antagonists & inhibitors*,  pharmacology
Rats, Wistar
Taurine / pharmacology*
beta-Alanine / pharmacology
gamma-Aminobutyric Acid / pharmacology
Reg. No./Substance:
0/Muscle Relaxants, Central; 107-35-7/Taurine; 107-95-9/beta-Alanine; 1134-47-0/Baclofen; 56-12-2/gamma-Aminobutyric Acid; 61-90-5/Leucine

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