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Drug–nutrient interactions: inhibition of amino acid intestinal absorption by fluoxetine

Published online by Cambridge University Press:  09 March 2007

Elena Urdaneta ,
Isabel Idoate  and
Jesús Larralde
Elena Urdaneta
Affiliation:
Departamento de Fisiología y Nutrición, Universidad de Navarra, C/Irunlarrea s/n, 31008 Pamplona, Spain
Isabel Idoate
Affiliation:
Departamento de Bioquímica, Hospital Virgen del Camino, C/Irunlarrea no. 4, 31008 Pamplona, Spain
Jesús Larralde*
Affiliation:
Departamento de Fisiología y Nutrición, Universidad de Navarra, C/Irunlarrea s/n, 31008 Pamplona, Spain
*
*Corresponding author: Dr Jésus Larralde, fax +34 48 425649; e-mail [email protected]
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Abstract

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Fluoxetine is one of the most widely used antidepressants and nowadays it is also being used to manage obesity problems. In our laboratory we demonstrated that the drug inhibited sugar absorption (Monteiro et al. 1993). The aim of the present work was to determine the effect of fluoxetine on intestinal leucine absorption. Using a procedure of successive absorptions in vivo the drug diminished amino acid absorption by 30% (P < 0.001). Experiments in vitro in isolated jejunum also revealed a reduction in leucine uptake of 37% (P < 0.001). In both cases fluoxetine only affected mediated transport without altering diffusion. In a preparation enriched in basolateral membrane, fluoxetine inhibited the Na+,K+-ATPase (EC 3.6.1.37) activity (55%; P < 0.001) in a non-competitive manner with an inhibition constant (Ki) value of 0.92 mm. Leucine uptake by brush-border membrane vesicles was diminished by the drug (a reduction of 48% was observed at 30s, P < 0.001); only the apical Na+-dependent transport system of the amino acid was modified and the inhibition was non-competitive. Leucine uptake in the presence of lysine indicated that transporter B was involved. These results suggest that fluoxetine reduces leucine absorption by its action on the basolateral and apical membrane of the enterocyte; the nutritional status of the patients under drug treatment may be affected as neutral amino acid absorption is decreased.

Keywords

FluoxetineDrug-nutrient interactionsIntestinal absorption
Type
General Nutrition
Information
British Journal of Nutrition , Volume 79 , Issue 5 , May 1998 , pp. 439 - 446
Copyright
Copyright © The Nutrition Society 1998

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