introduction: hyperprolactinemia is a common serious side effect of antipsychotic medications that are currently used in the treatment of patients with schizophrenia. pharmacogenetic approaches offer the possibility of identifying patient-specific biomarkers for predicting the risk of this side effect. we investigated a possible relationship between variants (snps) in genes for cytochrome 2d6 (...

background: cyp2d6 is polymorphically expressed enzyme that show marked interindividual and interethnic variation. phenotyping of cyp2d6 provides valuable information about real-time activity of this important drug-metabolizing enzymes through the use of specific probe drugs. the aim of this study was to identify the cyp2d6 oxidation phenotype with dextromethorphan (dex) as a probe drug in maza...

BACKGROUND Cytochrome P450 2D6 (CYP2D6), one of the most important drug-metabolizing enzymes, has been reported to possess variation in the encoding CYP2D6 gene (cytochrome P450, family 2, subfamily D, polypeptide 6) that affects enzymatic activity. For the pharmacogenetic study of CYP2D6, accurate measurement of the dosage of the functional gene is essential; however, current genotyping techni...

Cytochrome P450 2D6 (CYP2D6) has been identified as the major autoantigen in type 2 autoimmune hepatitis (AIH). However, because of a lack of appropriate animal models, the etiology of AIH is still poorly understood. We generated a mouse model for AIH using the human CYP2D6 as a triggering molecule for autoimmunity. We infected wild-type FVB mice with an adenovirus expressing human CYP2D6 (Ad-2...

AIM We evaluated single nucleotide polymorphisms (SNPs) of CYP2D6 to identify those that influence the efficiency of tamoxifen in adjuvant treatment of breast cancer through a matched case-control study. METHODS Peripheral blood DNA was collected from 20 patients with disease recurrence during adjuvant tamoxifen treatment and from 19 patients who had completed 5 years of tamoxifen therapy wit...

Upon characterization of baculovirus-expressed cytochrome P-450 (CYP) 2C19, it was observed that this enzyme metabolized (+/-) bufuralol to 1'hydroxybufuralol, a reaction previously understood to be selectively catalyzed by CYP2D6. The apparent K(m) for this reaction was 36 microM with recombinant CYP2C19, approximately 7-fold higher than for recombinant CYP2D6. The intrinsic clearance for this...

Within the human cytochrome P450 family, specific forms show developmental expression patterns that can affect drug clearance, efficacy, and safety. The objective of this study was to use dextromethorphan O-demethylase activity and quantitative Western blotting to identify CYP2D6 developmental expression patterns in a large (n = 222) and developmentally diverse set of pediatric liver samples. I...

The well described genetic polymorphism of the CYP2D6 gene influences response to a wide variety of therapeutic agents metabolized by the CYP2D6 enzyme product. CYP2D6 also appears to play a role, along with other cytochrome P450 enzymes, in the metabolic activation of the tobacco specific nitrosamine, NNK, as well as metabolism of nicotine to cotinine. While impaired activity of CYP2D6 was str...

The formation of R- and S-norfluoxetine was analyzed in vitro in human liver microsomes. Low apparent K(m) values for R-norfluoxetine formation of < or =8 microM and S-norfluoxetine of <0.2 microM were determined. R-Norfluoxetine formation rates in a characterized microsomal bank correlated with the catalytic activities for cytochrome P450 (CYP) 2D6, CYP2C9, and CYP2C8. Expressed CYP2C9, CYP2C1...

SCH 66712 [5-fluoro-2-[4-[(2-phenyl-1H-imidazol-5-yl)methyl]-1-piperazinyl]pyrimidine] caused a time- and NADPH-dependent loss of CYP2D6 activity. The inactivation of human liver (HL) microsomal dextromethorphan O-demethylase activity, a prototype marker for CYP2D6, was characterized by a K(I) of 4.8 microM and a maximal rate constant of inactivation (k(inact)) of 0.14 min(-1). The inactivation...