Eshelman School of Pharmacy, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
J Clin Pharmacol. 2013 Sep;53(9):982-90. doi: 10.1002/jcph.136. Epub 2013 Jul 23.
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 C(max) 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.
葡萄柚汁（GFJ）-非索非那定相互作用涉及抑制肠道有机阴离子转运多肽（OATP）介导的摄取。只有柚皮苷在临床上被证明能抑制肠道 OATP；其他成分尚未进行评估。与原始果汁相比，比较了不含呋喃香豆素（99%）和多甲氧基黄酮（90%）的改良 GFJ 对非索非那定分布的影响。两种果汁的提取物在 OATP 转染细胞中以相似的程度抑制雌酮 3-硫酸盐和非索非那定摄取（分别为50%和25%）。健康志愿者（n = 18）按随机、三向交叉设计接受水、GFJ 或改良 GFJ（240 毫升）给予非索非那定（120 毫克）。与水相比，两种果汁均使非索非那定几何平均 AUC 和 C(max)降低约 25%（P ≤.008 和 P ≤.011，分别），对终末半衰期无影响（P =.11）。两种果汁对非索非那定药代动力学的相似影响表明，呋喃香豆素和多甲氧基黄酮不是 GFJ-非索非那定相互作用的主要介导物。
