The grapefruit juice (GFJ)–fexofenadine interaction involves inhibition of intestinal organic anion transporting polypeptide (OATP)-mediated uptake. Only naringin has been shown clinically to inhibit intestinal OATP; other constituents have not been evaluated. The effects of a modified GFJ devoid of furanocoumarins (˜99%) and polymethoxyflavones (˜90%) on fexofenadine disposition were compared to effects of the original juice. Extracts of both juices inhibited estrone 3-sulfate and fexofenadine uptake by similar extents in OATP-transfected cells (˜50% and ˜25%, respectively). Healthy volunteers (n = 18) were administered fexofenadine (120 mg) with water, GFJ, or modified GFJ (240 mL) by randomized, three-way crossover design. Compared to water, both juices decreased fexofenadine geometric mean AUC and Cmax by ˜25% (P ≤ .008 and P ≤ .011, respectively), with no effect on terminal half-life (P = .11). Similar effects by both juices on fexofenadine pharmacokinetics indicate furanocoumarins and polymethoxyflavones are not major mediators of the GFJ–fexofenadine interaction.