This study was conducted to investigate the effect of the reduced function allele CYP2D6*10, which can be the cause of an intermediate metabolizer (IM), on tolterodine pharmacokinetics. Tolterodine is mainly metabolized to an active 5-hydroxymethyl metabolite (5-HM) by CYP2D6, and 5-HM is also metabolized by CYP2D6. Asian and white healthy volunteers (n = 108) received once daily multiple doses...

Introduction Cytochrome P450 2D6 (CYP2D6) is a clinically important CYP, metabolising approximately 25% common drugs. We investigated the clinical effect of acute kidney injury (AKI) on hepatic CYP2D6 metabolism in critically ill adults, using the probe drug tramadol (abstract 470). We found no effect of AKI but a strong CYP2D6 genotype/phenotype influence on tramadol metabolism. Rodent studies...

Formalin-fixed, paraffin-embedded tumors (FFPETs) are a valuable source of DNA for genotype association studies and are often the only germline DNA resource from cancer clinical trials. The anti-estrogen tamoxifen is metabolized into endoxifen by CYP2D6, leading to the hypothesis that patients with certain CYP2D6 genotypes may not receive benefit because of their inability to activate the drug....

PURPOSE Genetic variation in cytochrome P450 2D6 (CYP2D6) and the gene expression ratio of the homeobox 13 (HOXB13) to interleukin-17B receptor (IL17BR) are associated with tamoxifen resistance. We sought to determine the combined effect of inherited (CYP2D6) and somatic (HOXB13/IL17BR) gene variation in tamoxifen-treated breast cancer. EXPERIMENTAL DESIGN Retrospective analysis of women with...

Cytochrome P450 2D6 (CYP2D6), a major drug-metabolizing enzyme, is responsible for metabolism of approximately 25% of marketed drugs. Clinical evidence indicates that metabolism of CYP2D6 substrates is increased during pregnancy, but the underlying mechanisms remain unclear. To identify transcription factors potentially responsible for CYP2D6 induction during pregnancy, a panel of genes differe...

BACKGROUND The genetically polymorphic cytochrome P450 2D6 isozyme (CYP2D6) is responsible for the metabolism of numerous psychotropic medications pertinent to the practice of geriatric psychiatry. Optimal use of psychotropics in the elderly requires a thorough understanding of the determinants of marked variability in plasma concentrations. This review article will focus on basic pharmacokinet...

Genotype/phenotype analysis with human hepatocytes has identified a new inactive CYP2D6 allele, CYP2D6*56. Cryopreserved human hepatocytes from 51 livers were evaluated for CYP2D6 activity with dextromethorphan as the probe substrate. Hepatocyte lots that lacked CYP2D6 activity were further evaluated for CYP2D6 expression and known genetic variations, including CYP2D6*2, *3, *4, *5, *6, *7, *8,...

Cholestasis activates bile acid receptor farnesoid X receptor (FXR) and subsequently enhances hepatic expression of small heterodimer partner (SHP). We previously demonstrated that SHP represses the transactivation of cytochrome P450 2D6 (CYP2D6) promoter by hepatocyte nuclear factor (HNF) 4α. In this study, we investigated the effects of estrogen-induced cholestasis on CYP2D6 expression. Estro...

The stereoselective pharmacokinetic of Tramadol (T) and its main metabolites concerning the influence of CYP2D6 phenotype and gender on the phase I metabolism of this compound was studied after administration of 100 mg single oral dose of racemic T to 24 male and female subjects. The pharmacokinetic parameters were estimated from plasma concentrations of the analytes enantiomers. The metabolic ...

BACKGROUND CYP2D6 is considered the key enzyme in tamoxifen metabolism. Several studies have investigated the relationship between the CYP2D6 genotype and tamoxifen treatment outcome, with discrepant results. CYP2D6 inhibitor use, aromatase inhibitor use, and chemotherapy may account for some of the discrepancies. We examined the association between CYP2D6 genotype and early breast cancer event...