Related Experiment Videos
Fruit juices inhibit organic anion transporting polypeptide-mediated drug uptake to decrease the oral availability of
George K Dresser1, David G Bailey, Brenda F Leake
1Department of Medicine, University of Western Ontario, London, Ontario, Canada.
Clinical Pharmacology and Therapeutics
|February 2, 2002
Summary
Fruit juices, particularly grapefruit, significantly inhibit organic anion transporting polypeptides (OATPs), impacting drug absorption and bioavailability. This interaction highlights a key mechanism in food-drug interactions.
Area of Science:
- Pharmacology
- Drug Metabolism
- Nutritional Science
Background:
- Drug transporters like P-glycoprotein and OATPs influence drug absorption and efficacy.
- Food-drug interactions can alter drug disposition, affecting therapeutic outcomes.
Purpose of the Study:
- To investigate the in vitro effects of various fruit juices and their components on P-glycoprotein and OATP activity.
- To assess the in vivo impact of fruit juices on the oral pharmacokinetics of fexofenadine in humans.
Main Methods:
- In vitro assays using cell monolayers to measure P-glycoprotein efflux and OATP uptake.
- A randomized crossover study in healthy subjects evaluating fexofenadine pharmacokinetics with water and different fruit juices.
Main Results:
- Fruit juices, especially grapefruit and apple, significantly inhibited OATP activity but not P-glycoprotein activity.
- In vivo, grapefruit, orange, and apple juices reduced fexofenadine bioavailability (AUC, Cmax) by 60-70% compared to water.
- Specific compounds like 6',7'-Dihydroxybergamottin were identified as potent OATP inhibitors.
Conclusions:
- Fruit juices are more potent inhibitors of OATPs than P-glycoprotein.
- These interactions can significantly reduce oral drug bioavailability, influencing drug efficacy.
- Findings support a novel model for intestinal drug absorption and food-drug interactions.