Slide 19 of 76
Notes:
- P-glycoprotein (P-gp) is an ATP-dependent, efflux membrane transporter
- Originally detected in numerous tumor cell types, and implicated in the role of multidrug (MDR) resistance
- P-gp expells drug from cells, resulting in decreased intracellular drug concentrations, and consequently decreased antitumor activity
- In addition, P-glycoprotein is present in tissues:
- epithelial cells of the gastrointestinal tract, liver, and kidney
- expressed at level of the blood-brain barrier
- also noted in subsets of CD4+ T lymphocytes
- P-gp has broad substrate specificity, and appears to play a role in the transport of many natural substances and xenobiotics, includingchloride ions, hormones, peptides, cardiac glycosides, antitumour drugs, fluorescent dyes.
- Now being increasingly recognized as having a role in pharmacokinetics of many medications, including protease inhibitors
- Also preliminary data to suggest that P-gp expression may be associated with HIV replication. Observations from small studies revealed that patients with good virologic control had higher levels of P-gp expression than those who remained viremic. These data require further study and verification, but nonetheless, it is evident that P-gp can impact many aspects of HIV disease.
Back DJ, Jones K, Hennessy M, et al. Potential clinical relevance of drug transporters in antiretroviral pharmacology. Program and abstracts of the 8th Conference on Retroviruses and Opportunistic Infections; February 4-8, 2001; Chicago, Illinois. Abstract S3
