Role of P-glycoprotein in drug disposition

Research output: Contribution to journalArticle

180 Citations (Scopus)

Abstract

P-glycoprotein (Pgp), which is coded by human MDR1 (multidrug resistance) gene, is an energy-dependent efflux pump that exports its substrates out of the cell. Human Pgp is present not only in tumor cells but also in normal tissue including the kidney, liver, small and large intestine, brain, testis, and adrenal gland, and the pregnant uterus. This tissue distribution indicates that Pgp plays a significant role in excreting xenobiotics and metabolites into urine and bile and into the intestinal lumen, and in preventing their accumulation in the brain. The roles of Pgp in drug disposition include a urinary excretion mechanism in the kidney, a biliary excretion mechanism in the liver, an absorption barrier and determinant of oral bioavailability, and the blood-brain barrier that limits the accumulation of drugs in the brain. The inhibition of the transporting function of Pgp can cause clinically significant drug interactions and can also increase the penetration of drugs into the brain and the accumulation of drugs in the brain. Digoxin is a typical substrate for Pgp, which regulates the renal tubular secretion and brain distribution of digoxin. At present, potent Pgp inhibitors are being investigated in clinical trials aimed at overcoming the intrinsic or acquired multidrug resistance of human cancers. The clinical application of these Pgp inhibitors should take into consideration the physiologic function of pgp.

Original languageEnglish
Pages (from-to)137-140
Number of pages4
JournalTherapeutic Drug Monitoring
Volume22
Issue number1
DOIs
Publication statusPublished - 2000

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P-Glycoprotein
Brain
Pharmaceutical Preparations
Digoxin
Kidney
Liver
Drug interactions
Tissue
MDR Genes
Large Intestine
Multiple Drug Resistance
Xenobiotics
Tissue Distribution
Substrates
Adrenal Glands
Metabolites
Blood-Brain Barrier
Drug Interactions
Bile
Biological Availability

Keywords

  • ABC transporter
  • Blood-brain barrier
  • Digoxin
  • Multidrug resistance
  • Renal excretion

ASJC Scopus subject areas

  • Toxicology
  • Health, Toxicology and Mutagenesis
  • Pharmacology
  • Biochemistry
  • Biochemistry, Genetics and Molecular Biology(all)
  • Pharmacology (medical)
  • Public Health, Environmental and Occupational Health

Cite this

Role of P-glycoprotein in drug disposition. / Tanigawara, Yusuke.

In: Therapeutic Drug Monitoring, Vol. 22, No. 1, 2000, p. 137-140.

Research output: Contribution to journalArticle

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