Document Detail

Fruit juice inhibition of uptake transport: a new type of food-drug interaction.
MedLine Citation:
PMID:  21039758     Owner:  NLM     Status:  MEDLINE    
A new type of interaction in which fruit juices diminish oral drug bioavailability through inhibition of uptake transport is the focus of this review. The discovery was based on an opposite to anticipated finding when assessing the possibility of grapefruit juice increasing oral fexofenadine bioavailability in humans through inhibition of intestinal MDR1-mediated efflux transport. In follow-up investigations, grapefruit or orange juice at low concentrations potentially and selectively inhibited in vitro OATP1A2-mediated uptake compared with MDR1-caused efflux substrate transport. These juices at high volume dramatically depressed oral fexofenadine bioavailability. Grapefruit was the representative juice to characterize the interaction subsequently. A volume-effect relationship study using a normal juice amount halved average fexofenadine absorption. Individual variability and reproducibility data indicated the clinical interaction involved direct inhibition of intestinal OATP1A2. Naringin was a major causal component suggesting that other flavonoids in fruits and vegetables might also produce the effect. Duration of juice clinical inhibition of fexofenadine absorption lasted more than 2 h but less than 4 h indicating the interaction was avoidable with appropriate interval of time between juice and drug consumption. Grapefruit juice lowered the oral bioavailability of several medications transported by OATP1A2 (acebutolol, celiprolol, fexofenadine, talinolol, L-thyroxine) while orange juice did the same for others (atenolol, celiprolol, ciprofloxacin, fexofenadine). Juice clinical inhibition of OATP2B1 was unresolved while that of OATP1B1 seemed unlikely. The interaction between grapefruit juice and etoposide also seemed relevant. Knowledge of both affected uptake transporter and drug hydrophilicity assisted prediction of the clinical interaction with grapefruit or orange juice.
David G Bailey
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Publication Detail:
Type:  Journal Article; Review    
Journal Detail:
Title:  British journal of clinical pharmacology     Volume:  70     ISSN:  1365-2125     ISO Abbreviation:  Br J Clin Pharmacol     Publication Date:  2010 Nov 
Date Detail:
Created Date:  2010-11-02     Completed Date:  2011-02-24     Revised Date:  2013-07-03    
Medline Journal Info:
Nlm Unique ID:  7503323     Medline TA:  Br J Clin Pharmacol     Country:  England    
Other Details:
Languages:  eng     Pagination:  645-55     Citation Subset:  IM    
Copyright Information:
© 2010 The Author. British Journal of Clinical Pharmacology © 2010 The British Pharmacological Society.
Department of Medicine and Lawson Health Research Institute, London Health Sciences Centre Department of Physiology & Pharmacology, University of Western Ontario, London, Ontario, Canada.
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MeSH Terms
Administration, Oral
Anti-Allergic Agents / pharmacokinetics*
Biological Availability
Citrus paradisi*
Food-Drug Interactions / physiology*
Histamine H1 Antagonists, Non-Sedating / pharmacokinetics*
Organic Anion Transporters / metabolism
Terfenadine / analogs & derivatives*,  pharmacokinetics
Reg. No./Substance:
0/Anti-Allergic Agents; 0/Histamine H1 Antagonists, Non-Sedating; 0/Organic Anion Transporters; 138452-21-8/fexofenadine; 50679-08-8/Terfenadine

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