Polymorphisms in the ABC drug transporter gene MDR1.
In addition to genetically variable metabolic enzymes such as Cyp p450 proteins, blood and tissue levels of many drugs are influenced by controlled transport across compartmental boundaries. Major determinants in these transport processes are ATP-dependent efflux pumps such as P-glycoprotein and related proteins (eg MRPs), which can influence the bioavailability and CNS concentrations, as well as disposition of drugs. In addition to its recognized role in the development of multiple chemotherapy resistances, experimental evidence for the relevant influence of the MDR1 gene encoded P-glycoprotein, on the pharmacology of many other drugs has been gathered by the analyses of knockout mice, as well as in clinical studies. Recently, functional genetic polymorphisms in the MDR1 gene have been identified which influence the distribution and bioavailability of PGP substrates.
Brinkmann
U
U
Epidauros Biotechnology, Pharmacogenetics Labs., Bernried, Germany. uli@epidauros.com
Eichelbaum
M
M
D000818:Animals; D001682:Biological Availability; D004351:Drug Resistance / Q000235:genetics; D019450:Genes, MDR / Q000235:genetics* / Q000502:physiology; D014644:Genetic Variation; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D011110:Polymorphism, Genetic