Journal article
Ingredients in Fruit Juices Interact with Dasatinib Through Inhibition of BCRP: A New Mechanism of Beverage-Drug Interaction
Journal of pharmaceutical sciences, Vol.104(1), pp.266-275
01/2015
DOI: 10.1002/jps.24289
PMID: 25418056
Abstract
Small molecule tyrosine kinase inhibitors (TKIs) are a group of highly novel and target-specific anticancer drugs. Recently, most TKIs are found to be substrates of P-glycoprotein (P-gp) and Breast Cancer Resistance Protein (BCRP). However, little information is available regarding the Pgp- or BCRP-mediated interaction of TKIs with coadministered drugs/food/beverage. Our objective was to evaluate the effect of the major ingredients of grapefruit juice (GFJ), orange juice (OJ), apple juice (AJ), and green tea on P-gp and BCRP-mediated dasatinib efflux. Among the 14 ingredients screened, only tangeretin and nobiletin moderately inhibited P-gp-mediated dasatinib efflux. In contrast, four ingredients in GFJ [i.e., bergamottin, 6′,7′-dihydroxybergamottin (DHB), quercetin, and kaempferol], two ingredients in OJ (tangeretin and nobiletin), and one ingredient in AJ (i.e., hesperetin) greatly inhibited BCRP-mediated dasatinib efflux at the concentration of 50μM (p<0.001). Further concentration-dependent studies revealed that bergamottin, DHB, tangeretin, and nobiletin are potent BCRP inhibitors, with IC50 values 3.19, 5.2, 1.19, and 1.04μM, respectively. Further in vivo investigations are warranted to evaluate the BCRP-mediated FJ-TKI interaction. Literature reports only documented the modulatory effect of FJ and green tea on CYP3A, P-gp, and OATP. Our novel finding that FJ ingredients strongly inhibit BCRP may represent a new mechanism of beverage-drug interaction.
Details
- Title: Subtitle
- Ingredients in Fruit Juices Interact with Dasatinib Through Inhibition of BCRP: A New Mechanism of Beverage-Drug Interaction
- Creators
- Brett Fleisher - College of Pharmacy, University of Florida, Orlando, FloridaJesse Unum - College of Pharmacy, University of Florida, Orlando, FloridaJie Shao - Department of Pharmaceutics, College of Pharmacy, University of Florida, Orlando, FloridaGuohua An - Department of Pharmaceutics, College of Pharmacy, University of Florida, Orlando, Florida
- Resource Type
- Journal article
- Publication Details
- Journal of pharmaceutical sciences, Vol.104(1), pp.266-275
- DOI
- 10.1002/jps.24289
- PMID
- 25418056
- NLM abbreviation
- J Pharm Sci
- ISSN
- 0022-3549
- eISSN
- 1520-6017
- Publisher
- Elsevier Inc
- Grant note
- DOI: 10.13039/100001797, name: PhRMA Foundation; name: Start-up Fund from University of Florida
- Language
- English
- Date published
- 01/2015
- Academic Unit
- Pharmaceutical Sciences and Experimental Therapeutics
- Record Identifier
- 9984065313202771
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