A Modified Grapefruit Juice Eliminates Two Compound Classes as Major Mediators of the Grapefruit Juice-Fexofenadine Interaction: An In Vitro-In Vivo %26quot;Connect%26quot;

作者：Won Christina S; Lan Tian; VanderMolen Karen M; Dawson Paul A; Oberlies Nicholas H; Widmer Wilbur W; Scarlett Yolanda V; Paine Mary F^*

来源：The Journal of Clinical Pharmacology, 2013, 53(9): 982-990.

DOI：10.1002/jcph.136

• clinical pharmacology
• clinical research
• gastrointestinal
• pharmacokinetics and drug metabolism

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.

• 出版日期2013-9