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


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Lee
Caroline A
CA
Pfizer Global Research & Development, Department of Pharmacokinetics, Dynamics & Metabolism, 10646 Science Center Drive, San Diego, CA 92121, USA. caroline.lee01@pfizer.com
Cook
Jack A
JA
Reyner
Eric L
EL
Smith
Dennis A
DA
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001665:Binding Sites; D001692:Biological Transport; D004077:Digoxin / Q000493:pharmacokinetics; D004347:Drug Interactions; D015870:Gene Expression; D006801:Humans; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D011110:Polymorphism, Genetic; D011485:Protein Binding
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D004364:Pharmaceutical Preparations; D004077:Digoxin