A Modified Grapefruit Juice Eliminates Two Compound Classes as Major Mediators of the Grapefruit Juice–Fexofenadine Interaction: An In Vitro–In Vivo “Connect”

UNCG Author/Contributor (non-UNCG co-authors, if there are any, appear on document)
Nicholas Oberlies, Patricia A. Sullivan Distinguished Professor of Chemistry (Creator)
Institution
The University of North Carolina at Greensboro (UNCG )
Web Site: http://library.uncg.edu/

Abstract: 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.

Additional Information

Publication
The Journal of Clinical Pharmacology, 53(9), 982–990
Language: English
Date: 2013
Keywords
clinical pharmacology, clinical research, gastrointestinal, pharmacokinetics, drug metabolism

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