title: pH and energy dependent transport of ketoprofen across rat jejunum in vitro.
abstract: The aim of this study was to elucidate transport mechanisms of ketoprofen (monocarboxylic acid with pK(a) 4.6) across rat jejunum in vitro using side-by-side diffusion cells. When the tissue was incubated on the mucosal and serosal sides with buffer of pH 7.51 (pH of the mucosal surface was 7.08), ketoprofen permeated faster in the mucosal-to-serosal than in the opposite direction. No asymmetry in transport was observed when 2 mM mucus disrupting agent 1,4-dithio-DL-threitol (pH of the mucosal surface increased to 7.21) was added to the mucosal side. Mucosal-to-serosal permeability of ketoprofen increased three times when the pH of the incubation medium was changed from 8.06 (pH of the mucosal surface was 7.34) to 6.07 (pH of the mucosal surface was 5.95), while no pH dependence was found under ATP-depletion caused by sodium azide. In the ketoprofen concentration range from 0.125 to 5 mM no saturation of transport was observed. Moreover, ketoprofen transport was not changed in the presence of 2 mM benzoate, 10 and 20 mM acetate, 20 mM L-lactate (substrates for monocarboxylate transporter 1, MCT1) and 1 mM alpha-cyano-4-hydroxy-cinnamic acid (an inhibitor of MCT1). These results indicate that ketoprofen is transported across rat jejunum in vitro by pH and energy dependent transport mechanisms, and most probably not by MCT1.
authors.affiliation: Faculty of Pharmacy, University of Ljubljana, Ljubljana, Slovenia.
authors.forename: Igor
authors.initials: I
authors.lastname: Legen
authors.forename: Albin
authors.initials: A
authors.lastname: Kristl
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000493:pharmacokinetics*; D001693:Biological Transport, Active / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D003373:Coumaric Acids / Q000493:pharmacokinetics; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D007413:Intestinal Mucosa / Q000378:metabolism; D007583:Jejunum / Q000378:metabolism*; D007660:Ketoprofen / Q000493:pharmacokinetics*; D008297:Male; D027501:Monocarboxylic Acid Transporters / Q000037:antagonists & inhibitors / Q000378:metabolism; D010539:Permeability; D051381:Rats; D017208:Rats, Wistar; D019810:Sodium Azide / Q000494:pharmacology; D020160:Sodium Benzoate / Q000494:pharmacology; D019354:Sodium Lactate / Q000494:pharmacology; D027981:Symporters / Q000037:antagonists & inhibitors / Q000378:metabolism; D013997:Time Factors; D000099233:Monocarboxylate Transport Protein 1
chemical_list: D000255:Adenosine Triphosphate; D000894:Anti-Inflammatory Agents, Non-Steroidal; D003373:Coumaric Acids; D007660:Ketoprofen; D027501:Monocarboxylic Acid Transporters; D019810:Sodium Azide; D020160:Sodium Benzoate; D019354:Sodium Lactate; D027981:Symporters; D000099233:Monocarboxylate Transport Protein 1; C007175:alpha-cyano-4-hydroxycinnamate