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.
A Modified Grapefruit Juice Eliminates Two Compound Classes as Major Mediators of the Grapefruit Juice–Fexofenadine Interaction: An In Vitro–In Vivo “Connect”
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Created on 4/30/2014
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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