P-glycoprotein related drug interactions: clinical importance and a consideration of disease states

Expert Opin Drug Metab Toxicol. 2010 May;6(5):603-19. doi: 10.1517/17425251003610640.


Importance of the field: P-glycoprotein (P-gp) is the most characterized drug transporter in terms of its clinical relevance for pharmacokinetic disposition and interaction with other medicines. Clinically significant P-gp related drug interactions appear restricted to digoxin. P-gp may act as a major barrier to current and effective drug treatment in a number of diseases including cancer, AIDS, Alzheimer's and epilepsy due to its expression in tumors, lymphocytes, cell membranes of brain capillaries and the choroid plexus.

Areas covered in this review: This review summarizes the current understanding of P-gp structure/function, clinical importance of P-gp related drug interactions and the modulatory role this transporter may contribute towards drug efficacy in disease states such as cancer, AIDS, Alzheimer's and epilepsy.

What the reader will gain: The reader will gain an understanding that the clinical relevance of P-gp in drug interactions is limited. In certain disease states, P-gp in barrier tissues can modulate changes in regional distribution.

Take home message: P-gp inhibition in isolation will not result in clinically important alterations in systemic exposure; however, P-gp transport may be of significance in barrier tissues (tumors, lymphocytes, brain) resulting in attenuated efficacy.

Publication types

  • Review

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / genetics
  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism*
  • Animals
  • Binding Sites
  • Biological Transport
  • Digoxin / pharmacokinetics
  • Drug Interactions
  • Gene Expression
  • Humans
  • Pharmaceutical Preparations / metabolism*
  • Polymorphism, Genetic
  • Protein Binding


  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Pharmaceutical Preparations
  • Digoxin