Anthocyanins are a class of flavonoids found in many berry fruits, including blueberries. Public interest in blueberries and other anthocyanin-containing products has increased in recent years due to their reported health-promoting properties. In turn, the concomitant consumption of anthocyanin-containing products with prescription drugs is likely to occur. Unfortunately, little information is currently available regarding the potential drug interaction risks associated with anthocyanins. The objective of this application is to establish the effects of anthocyanins on the cytochrome P450 (CYP) enzymes and the drug transporter, P-glycoprotein.
In Aim 1, we will determine the potential of anthocyanins and anthocyanidins to inhibit CYP activity in vitro. In preliminary work, blueberry juice inhibited the in vitro activity of CYP3A and CYP2C9 at concentrations that could easily be achieved in the gastrointestinal tract after BBJ consumption. Consequently, in Aim 2, we will ascertain the clinical relevance of these in vitro interactions by conducting pharmacokinetic studies in which blueberry juice will be coadministered with the probe substrates buspirone (CYP3A) and flurbiprofen (CYP2C9). Since alterations in the activity of P-glycoprotein can also influence drug disposition, in Aim 3 we will examine the effects of anthocyanins and anthocyanidins on P-glycoprotein-mediated fexofenadine transport across Caco-2 cell monolayers. Taken together, the knowledge gained from these studies will help ensure the safe use of anthocyanin-containing products by the public.

Public Health Relevance

The results of this application will provide information for scientists and clinicians regarding the potential for drug-nutrient interactions to occur when patients concomitantly consume anthocyanin-containing preparations with their medications.

Agency
National Institute of Health (NIH)
Institute
National Center for Complementary & Alternative Medicine (NCCAM)
Type
Predoctoral Individual National Research Service Award (F31)
Project #
5F31AT006068-03
Application #
8274345
Study Section
Special Emphasis Panel (ZAT1-PK (08))
Program Officer
Hopp, Craig
Project Start
2010-04-15
Project End
2012-08-31
Budget Start
2012-04-15
Budget End
2012-08-31
Support Year
3
Fiscal Year
2012
Total Cost
$29,478
Indirect Cost
Name
Tufts University
Department
Pharmacology
Type
Schools of Medicine
DUNS #
039318308
City
Boston
State
MA
Country
United States
Zip Code
02111
Hanley, Michael J; Masse, Gina; Harmatz, Jerold S et al. (2013) Effect of blueberry juice on clearance of buspirone and flurbiprofen in human volunteers. Br J Clin Pharmacol 75:1041-52
Hanley, Michael J; Cancalon, Paul; Widmer, Wilbur W et al. (2011) The effect of grapefruit juice on drug disposition. Expert Opin Drug Metab Toxicol 7:267-86