Modulation of the activity of ABC transporters (P-glycoprotein, MRP2, BCRP) by flavonoids and drug response

J Pharm Sci. 2010 Feb;99(2):598-617. doi: 10.1002/jps.21851.

Abstract

The present article aims to review the up-to-date information on the most recent studies of the interaction of flavonoids with ABC transporters, in particular the drug pharmacokinetic consequences of such a relationship. In addition, the modulation of the expression of the ABC transporters by flavonoids is also illustrated. Flavonoids are a large group of plant polyphenols present extensively in our daily diets and herbal products. High intake of isoflavones has been associated with a variety of beneficial effects on several common diseases. These polyphenols interact with ABC drug transporters involved in drug resistance and drug absorption, distribution and excretion. A number of studies have demonstrated inhibition of drug transporters by flavonoids. This flavonoid-ABC-transporter interaction could be beneficial for poorly absorbed drugs but could also result in severe drug intoxication, especially drugs with a narrow therapeutic window. On the other hand, flavonoids are themselves substrates of ABC transporters. These proteins can affect the oral availability and tissue distribution of these compounds, modifying their beneficial effects. The challenge is to find a suitable way to predict harmful drug-flavonoid interactions mediated by these transporters.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / biosynthesis
  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / drug effects*
  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism*
  • ATP Binding Cassette Transporter, Subfamily G, Member 2
  • ATP-Binding Cassette Transporters / biosynthesis
  • ATP-Binding Cassette Transporters / drug effects*
  • ATP-Binding Cassette Transporters / metabolism*
  • Animals
  • Cytochrome P-450 Enzyme Inhibitors
  • Cytochrome P-450 Enzyme System / metabolism
  • Enzyme Inhibitors / pharmacology
  • Flavonoids / metabolism
  • Flavonoids / pharmacology*
  • Flavonoids / toxicity
  • Humans
  • Multidrug Resistance-Associated Proteins / biosynthesis
  • Multidrug Resistance-Associated Proteins / drug effects*
  • Multidrug Resistance-Associated Proteins / metabolism*
  • Neoplasm Proteins / biosynthesis
  • Neoplasm Proteins / drug effects*
  • Neoplasm Proteins / metabolism*

Substances

  • ABCG2 protein, human
  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • ATP Binding Cassette Transporter, Subfamily G, Member 2
  • ATP-Binding Cassette Transporters
  • Cytochrome P-450 Enzyme Inhibitors
  • Enzyme Inhibitors
  • Flavonoids
  • Multidrug Resistance-Associated Proteins
  • Neoplasm Proteins
  • multidrug resistance-associated protein 2
  • Cytochrome P-450 Enzyme System