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Functional polymorphisms of the human multidrug-resistance gene: multiple sequence variations and correlation of one allele with P-glycoprotein expression and activity in vivo.
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. Expand
Nuclear Receptor Response Elements Mediate Induction of Intestinal MDR1 by Rifampin*
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. Expand
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. Expand
The role of intestinal P-glycoprotein in the interaction of digoxin and rifampin.
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. Expand
Cytochrome P450 2D6: overview and update on pharmacology, genetics, biochemistry
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. Expand
Frequency of single nucleotide polymorphisms in the P‐glycoprotein drug transporter MDR1 gene in white subjects
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.Expand
Polymorphic Organic Anion Transporting Polypeptide 1B1 is a Major Determinant of Repaglinide Pharmacokinetics
The aim was to investigate possible associations between the pharmacokinetics of repaglinide and single nucleotide polymorphisms (SNPs) in the genes encoding for the drug transporters organic anion transporting polypeptide 1B1 and P‐glycoprotein and the drug‐metabolizing enzymes cytochrome P450 (CYP) 2C8 and CYP3A5. Expand
Antimalarial Artemisinin Drugs Induce Cytochrome P450 and MDR1 Expression by Activation of Xenosensors Pregnane X Receptor and Constitutive Androstane Receptor
Activation of PXR and CAR and especially the resulting induction of CYP3A4 and MDR1 demonstrate that artemisinin has a higher risk of potential drug interactions than anticipated previously. Expand
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
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. Expand
Potent Mechanism-Based Inhibition of Human CYP2B6 by Clopidogrel and Ticlopidine
Inhibition of CYP2B6 was time- and concentration-dependent, and as shown by dialysis experiments, it was irreversible and dependent on NADPH, suggesting a mechanism-based mode of action, and the possibility of drug interactions between thienopyridine derivates and drug substrates of CYp2B 6 and CYP1A2 is suggested. Expand