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Cytochrome P450 enzymes in drug metabolism: regulation of gene expression, enzyme activities, and impact of genetic variation.
Recent progress on drug metabolism activity profiles, interindividual variability and regulation of expression, and the functional and clinical impact of genetic variation in drug metabolizing P450s are reviewed. Expand
Cytochrome P450 2D6: overview and update on pharmacology, genetics, biochemistry
- U. Zanger, S. Raimundo, M. Eichelbaum
- Biology, Medicine
- Naunyn-Schmiedeberg's Archives of Pharmacology
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
The genetic determinants of the CYP3A5 polymorphism.
Investigation of the expression of CYP3A5 and its genetic determinants in a panel of 183 Caucasian liver samples reports that a SNP within intron 3 (g.6986G>A) is the primary cause of the CYP4A5 protein polymorphism, and should add to efforts to identify clinically relevant, CYP2A5-specific reactions and to further elucidate traits responsible for variable expression of the entire CYP 3A family. Expand
Functional pharmacogenetics/genomics of human cytochromes P450 involved in drug biotransformation
- U. Zanger, M. Turpeinen, K. Klein, M. Schwab
- Analytical and bioanalytical chemistry
- 10 August 2008
The elimination routes for the 200 drugs that are sold most often by prescription count in the United States were investigated and Clinically well-established polymorphic CYPs were involved in the metabolism of approximately half of those drugs, including NSAIDs metabolized mainly by CYP2C9, proton-pump inhibitors metabolized by CYD2C19, and beta blockers and several antipsychotics and antidepressants metabolizing by CYB2D6. Expand
Identification of the human cytochromes P450 involved in the oxidative metabolism of "Ecstasy"-related designer drugs.
It is concluded that, in addition to CP2D6 as the sole high-affinity demethylenase, several other P450 isozymes have the capacity to contribute to microsomal oxidative metabolism of methylenedioxyamphetamines. Expand
Polymorphic CYP2B6: molecular mechanisms and emerging clinical significance.
- U. Zanger, K. Klein, T. Saussele, J. Blievernicht, M. Hofmann, M. Schwab
- Biology, Medicine
- 18 July 2007
General biomolecular and pharmacological features are summarized and a detailed up-to-date description of genetic polymorphisms are presented, including a discussion of recent clinical applications of CYP2B6 pharmacogenetics. Expand
Potent Mechanism-Based Inhibition of Human CYP2B6 by Clopidogrel and Ticlopidine
- T. Richter, T. Mürdter, +5 authors U. Zanger
- Chemistry, Medicine
- Journal of Pharmacology and Experimental…
- 1 January 2004
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
Expression of organic cation transporters OCT1 (SLC22A1) and OCT3 (SLC22A3) is affected by genetic factors and cholestasis in human liver
Cholestasis and genetic variants are identified as critical determinants for considerable interindividual variability of hepatic OCT1 and OCT3 expression and consequences for hepatic elimination of and response to OCT substrates such as metformin are indicated. Expand
Sex is a major determinant of CYP3A4 expression in human liver
Sex, in addition to PXR and drug exposure, is a major factor for CYP3A4 expression in humans, thus explaining many of the previous observations of sex‐dependent drug clearance. Expand
Comprehensive analysis of thiopurine S-methyltransferase phenotype-genotype correlation in a large population of German-Caucasians and identification of novel TPMT variants.
The results of this study provide a solid basis to predict TPMT phenotype in a Northern European Caucasian population by molecular diagnostics. Expand