Pharmacogenetics of the human drug-transporter gene MDR1: impact of polymorphisms on pharmacotherapy

• Published in: Drug Discovery Today Vol. 6; no. 16; pp. 835 - 839
• Main Authors: Brinkmann, Ulrich, Roots, Ivar, Eichelbaum, Michel
• Format: Book Review Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 15.08.2001; Elsevier Science
• Subjects: Biological and medical sciences; General pharmacology; MDR1; Medical sciences; multidrug resistance; P-glycoprotein; Pharmacokinetics. Pharmacogenetics. Drug-receptor interactions; Pharmacology. Drug treatments; pharmacotherapy; polymorphisms; P-glycoprotein; multidrug resistance; MDR1; Cancer biology; pharmacotherapy; Biochemistry; Molecular Medicine; polymorphisms; Drug Discovery; Human; Pharmacogenetics; Biological transport; P Glycoprotein; Transgenic animal; Review; Gene expression; In vitro; Conveyor; Resistance; In vivo; Gene; Animal; Genetics; Polymorphism
• ISSN: 1359-6446; 1878-5832
• DOI: 10.1016/S1359-6446(01)01892-X

The blood- and tissue-concentrations, and thus the activity, of many drugs are influenced by factors that are subject to inter-individual variation. Variables that influence blood levels are metabolizing enzymes and transporters. Transporters control drug uptake, distribution and elimination. Transport by efflux pumps such as MDR1-encoded P-glycoprotein can influence the bioavailability of drugs. Knowledge of the transporter ‘status’ might allow for compensation of differences in drug uptake, such as by dose adjustment, which is important for drugs with narrow therapeutic windows. So far, intestinal expression of MDR1 has been determined by cumbersome methods, such as biopsies, although recently a functional polymorphism has been identified, which discriminates individual high or low-expressor alleles. As a result, clinical trials and therapy can be adapted to the ‘ MDR1-status’ of individual patients.