A Modified Grapefruit Juice Eliminates Two Compound Classes as Major Mediators of the Grapefruit Juice-Fexofenadine Interaction: an In Vitro-In Vivo ‘Connect’
Journal of clinical pharmacology, Vol.53(9), pp.982-990
09/2013
:
https://hdl.handle.net/2376/100834
: PMC4029847
: 23878024
The grapefruit juice-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 grapefruit juice 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, grapefruit juice, or modified grapefruit juice (240 ml) by randomized, three-way crossover design. Compared to water, both juices decreased fexofenadine geometric mean AUC and C
max
by ~25% (
p
≤0.008 and
p
≤0.011, respectively), with no effect on terminal half-life (
p
=0.11). Similar effects by both juices on fexofenadine pharmacokinetics indicate furanocoumarins and polymethoxyflavones are not major mediators of the grapefruit juice-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’
- Christina S Won - Eshelman School of Pharmacy, The University of North Carolina at Chapel Hill, Chapel Hill, NCTian Lan - Department of Internal Medicine, Section on Gastroenterology, Wake Forest University School of Medicine, Winston-Salem, NCKaren M VanderMolen - Department of Chemistry and Biochemistry, The University of North Carolina at Greensboro, Greensboro, NCPaul A Dawson - Department of Internal Medicine, Section on Gastroenterology, Wake Forest University School of Medicine, Winston-Salem, NCNicholas H Oberlies - Department of Chemistry and Biochemistry, The University of North Carolina at Greensboro, Greensboro, NCWilbur W Widmer - Citrus and Subtropical Products Laboratory, United States Department of Agriculture, Winter Haven, FLYolanda V Scarlett - School of Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, NCMary F Paine - Eshelman School of Pharmacy, The University of North Carolina at Chapel Hill, Chapel Hill, NC
- Journal of clinical pharmacology, Vol.53(9), pp.982-990
- Pharmaceutical Sciences, Department of
- Wiley
- 9
- R01 GM077482; R01 DK047987; UL1RR025747 / National Institutes of Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA R01DK047987 / NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK) UL1TR000083 / NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Center for Advancing Translational Sciences (NCATS) UL1RR025747 / NATIONAL CENTER FOR RESEARCH RESOURCES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Center for Research Resources (NCRR) R01GM077482 / NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of General Medical Sciences (NIGMS)
- 99900546658701842
- English
- Accepted manuscript