title: Inhibitory effect of caffeic acid on human organic anion transporters hOAT1 and hOAT3: a novel candidate for food-drug interaction.
abstract: Several kinds of food have been shown to influence the absorption and metabolism of drugs, although there is little information about their effect on the renal excretion of drugs. In this study, we performed uptake experiments using Xenopus laevis oocytes to assess the inhibitory effects of chlorogenic acid, caffeic acid and quinic acid, which are contained in coffee, fruits and vegetables, on human organic anion transporters hOAT1 and hOAT3; these transporters mediate renal tubular uptake of anionic drugs from blood. Injection of hOAT1 and hOAT3 cRNA into oocytes stimulated uptake of typical substrates of hOAT1 and hOAT3 (p-aminohippurate and estrone sulfate, respectively); among the three compounds tested, caffeic acid most strongly inhibited these transporters. The apparent 50% inhibitory concentrations of caffeic acid were estimated to be 16.6 µM for hOAT1 and 5.4 µM for hOAT3. Eadie-Hofstee plot analysis showed that caffeic acid inhibited both transporters in a competitive manner. In addition to the transport of p-aminohippurate and estrone sulfate, that of antifolates and antivirals was inhibited by caffeic acid. These findings show that caffeic acid has inhibitory potential against hOAT1 and hOAT3, suggesting that renal excretion of their substrates could be affected in patients consuming a diet including caffeic acid.
authors.affiliation: Laboratory of Clinical Pharmacodynamics, School of Pharmacy, Aichi Gakuin University, Nagoya, Japan. yuuwai@dpc.agu.ac.jp
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Uwai
authors.forename: Yukihiro
authors.initials: Y
authors.lastname: Ozeki
authors.forename: Tomonori
authors.initials: T
authors.lastname: Isaka
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Honjo
authors.forename: Kikuo
authors.initials: K
authors.lastname: Iwamoto
mesh_terms: D000212:Acyclovir / Q000031:analogs & derivatives / Q000378:metabolism; D000818:Animals; D002109:Caffeic Acids / Q000494:pharmacology*; D002726:Chlorogenic Acid / Q000494:pharmacology; D003069:Coffee / Q000737:chemistry; D004970:Estrone / Q000031:analogs & derivatives / Q000378:metabolism; D018565:Food-Drug Interactions; D005638:Fruit / Q000737:chemistry; D006147:Guanine; D006801:Humans; D020128:Inhibitory Concentration 50; D008727:Methotrexate / Q000378:metabolism; D009865:Oocytes / Q000187:drug effects / Q000378:metabolism; D027362:Organic Anion Transport Protein 1 / Q000037:antagonists & inhibitors* / Q000235:genetics; D029362:Organic Anion Transporters, Sodium-Independent / Q000037:antagonists & inhibitors* / Q000235:genetics; D011801:Quinic Acid / Q000494:pharmacology; D018075:RNA, Complementary / Q000494:pharmacology; D014675:Vegetables / Q000737:chemistry; D014982:Xenopus laevis; D010130:p-Aminohippuric Acid / Q000378:metabolism
chemical_list: D002109:Caffeic Acids; D003069:Coffee; D027362:Organic Anion Transport Protein 1; D029362:Organic Anion Transporters, Sodium-Independent; D018075:RNA, Complementary; C114338:organic anion transport protein 3; D011801:Quinic Acid; D004970:Estrone; D002726:Chlorogenic Acid; C053539:penciclovir; D006147:Guanine; C017296:estrone sulfate; C040048:caffeic acid; D000212:Acyclovir; D010130:p-Aminohippuric Acid; D008727:Methotrexate