Polymorphism of Human Cytochrome P450 2D6 and Its Clinical Significance

  title={Polymorphism of Human Cytochrome P450 2D6 and Its Clinical Significance},
  author={Shufeng Zhou},
  journal={Clinical Pharmacokinetics},
Cytochrome P450 (CYP) 2D6 is one of the most investigated CYPs in relation to genetic polymorphism, but accounts for only a small percentage of all hepatic CYPs (∼2–4%). There is a large interindividual variation in the enzyme activity of CYP2D6. The enzyme is largely non-inducible and metabolizes ∼25% of current drugs. Typical substrates for CYP2D6 are largely lipophilic bases and include some antidepressants, antipsychotics, antiarrhythmics, antiemetics, β-adrenoceptor antagonists (β-blockers… 

Complexities of CYP2D6 gene analysis and interpretation

  • A. Gaedigk
  • Biology
    International review of psychiatry
  • 2013
A summary of the intricacies of CYP2D6 variation and genotype analysis is provided, knowledge that is invaluable for the translation of genotype into clinically useful information.

Role of cytochrome P450 2D6 genetic polymorphism in carvedilol hydroxylation in vitro

The present data in vitro suggest that the newly found variants significantly reduced catalytic activities compared with CYP2D6.1.2, which is greatly relevant to personalized medicine.

Identification of CYP2D6 allelic mutations in a sub-set of Karachi population

Evaluated gene and genotypic frequencies of CYP2D6 *1 extensive metabolizer, *4 poor metabolizer and *10 intermediate metabolizer allelic variants among depressed patients and compared with normal subjects and other populations demonstrate pronounced association of CYp2D 6 *4 and*10 allelic variant with patient’s drug response activity.

CYP2D6 and pharmacogenomics: where does future research need to focus? Part 2: clinical aspects.

The CYP2D6 enzyme contributes to the metabolism and bioactivation of approximately a quarter of drugs clinically used, including many antidepressants and antipsychotics, codeine and tramadol

CYP2D6 and pharmacogenomics: where does future research need to focus? Part 1: technical aspects.

The CYP2D6 enzyme contributes to the metabolism and bioactivation of approximately a quarter of drugs clinically used, including many antidepressants and antipsychotics, codeine and tramadol

CYP2D6 variability in populations from Venezuela

There is a considerable amount of work remaining before CYP2D6 is integrated into clinical practice in Venezuela, and it is necessary to increase research in this regard, in particular to develop studies with a larger sample size.

Effects of 24 CYP2D6 Variants Found in the Chinese Population on the Metabolism of Risperidone

This is the first report of all these novel alleles for risperidone metabolism, providing fundamental data for further clinical studies on CYP2D6 alleles.

Relationship of CYP2D6, CYP3A, POR, and ABCB1 Genotypes With Galantamine Plasma Concentrations

The CYP2D6 genotype seemed to be an important determinant of galantamine pharmacokinetics, with CYP 2D6 poor metabolizers presenting 45% and 61% higher dose-adjusted galantamines plasma concentrations than heterozygous and homozygous CYP3A extensive metabolizers.

Cytochrome P450 2D6 genotype–phenotype characterization through population pharmacokinetic modeling of tedatioxetine

The study provides new in vivo evidence of the enzyme function of different CYP2D6 genotype-phenotype relationships across substrates and suggests that the activity score assigned to the CYP 2D6*41 should be revisited, while CYP1D 6*17 appears to exhibit substrate-specific behaviour.



Polymorphisms in the CYP 2D6 Gene: Association with Plasma Concentrations of Fluoxetine and Paroxetine

It is found that plasma concentration of the antidepressant drugs was significantly correlated with genetic status and in PM fluoxetine-treated patients, drug plasma concentration was significantly higher than that seen in extensive metabolizers.

Genetic polymorphisms of cytochrome P450 2D6 (CYP2D6): clinical consequences, evolutionary aspects and functional diversity

Predictive CYP2D6 genotyping is estimated by the author to be beneficial for treatment of about 30–40% of CYP 2D6 drug substrates, that is, for about 7–10% of all drugs clinically used, although prospective clinical studies are necessary to evaluate the exact benefit of drug selection and dosage.

Polymorphic CYP2B6: molecular mechanisms and emerging clinical significance.

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.

Pharmacogenetics of cytochrome P4502D6: genetic background and clinical implication

  • I. Cascorbi
  • Biology
    European journal of clinical investigation
  • 2003
Since there is evidence that deteriorated drug elimination partly accounts for drug side‐effects, CYP2D6 genotyping could contribute to an individualized and therefore optimized drug therapy.

Comparative Metabolic Capabilities and Inhibitory Profiles of CYP2D6.1, CYP2D6.10, and CYP2D6.17

There are mixed effects on the functionally reduced allelic variants in enzyme-substrate affinity or enzyme-inhibitor affinity, which is lower, higher, or comparable to that for CYP2D6.1.

Cytochrome P450 2D6 variants in a Caucasian population: allele frequencies and phenotypic consequences.

A solid basis is provided for prediction of CYP2D6 capacity, as required in drug research and routine drug treatment, and significant differences in enzymatic activity measured by the dextromethorphan metabolic ratio (MR) are shown.

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.

CYP2D6 polymorphisms and the impact on tamoxifen therapy.

An overview of the history and application of CYP2D6 pharmacogenetics is provided, and the clinical implications of recent developments relating to the involvement of CY P450 2D6 in tamoxifen treatment are discussed.

Occurrence of CYP2D6 gene duplication in Hong Kong Chinese.

Establishing the prevalence of duplicated CYP2D6 active alleles may help prevent therapeutic failure in UM individuals treated with CYP 2D6 enzyme-substrates at standard doses.