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glycoprotein-P; MDR1; drug resistance

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Khaitovych, M. (2017). DRUG TRANSPORTER GLYCOPROTEIN-P: CLINICAL RELEVANCE. Medical Science of Ukraine (MSU), 12(1-2), 87-94. Retrieved from https://msu-journal.com/index.php/journal/article/view/115


Glycoprotein-P, the product of the MDR1 (ABCB1) gene, is an ATP-sensitive pump, that is expressed by polarization in plasmatic membrane of barrier cells and excretion organs, where it performs the function of protection and excretion, providing «ejection» into the extracellular space of various xenobiotics, including drugs.

Substrates of glycoprotein-P (antidepressants, cardiac glycosides, statins, cytostatics, antiretroviral drugs, etc.) may favorably be absorbed by the gastrointestinal tract, however, penetrating into the enterocytes they are immediately “ejected” by glycoprotein-P back to the intestinal lumen. In the hepatocytes glycoprotein-P actively secretes drugs into the bile; in the endotheliocytes of blood vessels of blood-brain barrier (BBB) –“ejects” drugs to the vessel lumen, preventing diffusion to the CNS; in the proximal renal tubules - secretes drugs in the urine. Some proportion of drugs – substrates of glycoprotein-P  also represents with CYP3A4 substrates, and these two systems (transport and metabolism of drugs) act coordinately. All these factors provide for decreased concentration of drugs- substrates in the blood.

The glycoprotein-P activity may be influenced by such factors: other drugs, herbal medicines and food products which are its inductors and inhibitors; genetic polymorphism of MDR1 gene. The latest researches have been shown overexpression of glycoprotein-P in BBB in case of depression and epilepsy resistant to therapy. Hyperexpression of glycoprotein-P in the lymphocytes is associated with activity of rheumatoid arthritis.

Conclusion. Glycoprotein-P may be considered as a perspective target for drug resistance management.

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