Food Additives Inhibit Intestinal Drug Transporters but Have Limited Effect on In Vitro Drug Permeability

Abstract

Food additives are chemical substances that are added to processed food to improve its flavor, texture, or appearance. Food additives can inhibit intestinal transporters, such as breast cancer resistance protein (BCRP), multidrug resistance associated protein 2 (MRP2), organic anion transporting polypeptide 2B1 (OATP2B1), and P-glycoprotein (P-gp). This inhibition could potentially affect the absorption of their substrate drugs and cause unwanted food–drug interactions. In this study, 22 food additives were evaluated for their impact on BCRP, MRP2, OATP2B1, and P-gp transport. The inhibition potency toward intestinal transporters was first studied using membrane vesicles and HEK293 cells. In these assays, four food additives (beta-carotene, butylated hydroxytoluene, dodecyl gallate, and octyl gallate) were identified as inhibitors. Seven food additives (allura red AC, beta-carotene, brilliant blue FCF, carmoisine, neohesperidin DC, sunset yellow FCF, and tartrazine), which were identified as inhibitors either in the current study or in our previous studies, were selected for Caco-2 permeability studies to further evaluate their possible effect on drug absorption. None of the selected food additives showed any effect on sulfasalazine permeability. These results suggest that the selected food additives are inhibitors of the studied transporters but are unlikely to cause clinically significant intestinal transporter-mediated drug interactions.