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.
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.
| 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, M J; Masse, G; Harmatz, J S et al. (2012) Pomegranate juice and pomegranate extract do not impair oral clearance of flurbiprofen in human volunteers: divergence from in vitro results. Clin Pharmacol Ther 92:651-7 |
| Greenblatt, David J; Zhao, Yanli; Hanley, Michael J et al. (2012) Mechanism-based inhibition of human cytochrome P450-3A activity by grapefruit hybrids having low furanocoumarin content. Xenobiotica 42:1163-9 |
| 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 |
