Functional polymorphisms of the human multidrug-resistance gene: multiple sequence variations and correlation of one allele with P-glycoprotein expression and activity in vivo.
- S. Hoffmeyer, O. Burk, U. Brinkmann
- Biology, MedicineProceedings of the National Academy of Sciences…
- 28 March 2000
A significant correlation of a polymorphism in exon 26 (C3435T) of MDR-1 with expression levels and function is observed and this polymorphism is expected to affect the absorption and tissue concentrations of numerous other substrates of M DR-1.
Nuclear Receptor Response Elements Mediate Induction of Intestinal MDR1 by Rifampin*
- A. Geick, M. Eichelbaum, O. Burk
- Biology, MedicineJournal of Biological Chemistry
- 4 May 2001
Intestinal P-glycoprotein, which is encoded by the MDR1 gene, plays an important role in the absorption and presystemic elimination of many xenobiotics, and its induction is mediated by a DR4 motif in the upstream enhancer at about −8 kilobase pairs, to which PXR binds.
The role of intestinal P-glycoprotein in the interaction of digoxin and rifampin.
- B. Greiner, M. Eichelbaum, H. Kroemer
- Medicine, BiologyJournal of Clinical Investigation
- 15 July 1999
Concomitant administration of rifampin reduced digoxin plasma concentrations substantially after oral administration but to a lesser extent after intravenous administration, and induction of intestinal P-gp could explain this new type of drug-drug interaction.
Cytochrome P450 2D6: overview and update on pharmacology, genetics, biochemistry
- U. Zanger, S. Raimundo, M. Eichelbaum
- BiologyNaunyn-Schmiedeberg's Archives of Pharmacology
- 2003
The intricate genetics of the CYP2D6 polymorphism is becoming apparent at ever greater detail, applications in clinical practice are still rare, and more clinical studies are needed to show where patients benefit from drug dose adjustment based on their genotype.
Extensive genetic polymorphism in the human CYP2B6 gene with impact on expression and function in human liver.
Significant reduced CYP2B6 protein expression and S-mephenytoin N-demethylase activity were found in carriers of the C1459T (R487C) mutation, demonstrating that the extensive interindividual variability of CYP 2B6 expression and function is not only due to regulatory phenomena, but also caused by a common genetic polymorphism.
Frequency of single nucleotide polymorphisms in the P‐glycoprotein drug transporter MDR1 gene in white subjects
- I. Cascorbi, T. Gerloff, I. Roots
- Biology, MedicineClinical pharmacology and therapy
- 1 March 2001
P‐glycoprotein, the gene product of MDR1, confers multidrug resistance against antineoplastic agents but also plays an important role in the bioavailability of common drugs in medical treatment.…
Activity Levels of Tamoxifen Metabolites at the Estrogen Receptor and the Impact of Genetic Polymorphisms of Phase I and II Enzymes on Their Concentration Levels in Plasma
- T. Mürdter, W. Schroth, H. Brauch
- Biology, MedicineClinical pharmacology and therapy
- 1 May 2011
Among the poor metabolizers, 93% had (Z)‐endoxifen levels below IC90 values, underscoring the role of CYP2D6 deficiency in compromised tamoxIFen bioactivation, and carriers of reduced‐function CYp2C9 (*2, *3) alleles had lower plasma concentrations of active metabolites (P < 0.004), pointing to the roleof additional pathways.
Predictive Value of Known and Novel Alleles of CYP2B6 for Efavirenz Plasma Concentrations in HIV‐infected Individuals
CYP2B6 poor metabolizer genotypes explain to a large extent EFV pharmacokinetics and identify individuals at risk of extremely elevated EFV plasma levels.
Polymorphic Organic Anion Transporting Polypeptide 1B1 is a Major Determinant of Repaglinide Pharmacokinetics
- M. Niemi, J. Backman, P. Neuvonen
- Biology, ChemistryClinical pharmacology and therapy
- 1 June 2005
Genetic variability of CYP2B6 in populations of African and Asian origin: allele frequencies, novel functional variants, and possible implications for anti-HIV therapy with efavirenz
Heterologous expression in COS-1 cells revealed pronounced reduction in expression and/or bupropion hydroxylase activity for variants T168I, D257N, R336C and P428T, whereas the triple mutant 2B6.17 (T26S, D28G, R29T) appeared to be functionally normal and should be particularly relevant for anti-HIV-therapy with efavirenz.
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