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 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, mediating renal tubular uptake of anionic drugs from blood. Injection of hOAT1 and hOAT3 cRNA stimulated uptake of their typical substrates, p-aminohippurate and estrone sulfate, respectively, into oocytes, and caffeic acid among the three compounds strongly reduced these transports. 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 for hOAT1 and hOAT3, suggesting that renal excretion of their substrates would be affected in patients consuming a diet including caffeic acid.