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

Shen, Hong; He, Minxia M.; Liu, Houfu; Wrighton, Steven; Wang, Li; Guo, Bin; Li, Chuan

doi:10.1124/dmd.107.015354

Cited by 152 publications

(150 citation statements)

References 31 publications

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“…Polymorphisms in the cytochrome P450 2D6 (CYP2D6) gene are a major cause of pharmacokinetic variability in humans, and sufficient evidence suggests ethnic differences in the metabolism of antipsychotics between Asian and western populations [54,55]. For instance, fluoxetine and paroxetine, which are potent CYP2D6 inhibitors, will raise aripiprazole blood levels and thus a lower dose might be used in clinical practice.…”

Section: Clinical Issues In the Use Of Atypical Antipsychotics In CLImentioning

confidence: 99%

Clinical Issues in Use of Atypical Antipsychotics for Depressed Patients

Pae

Patkar

2013

CNS Drugs

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Major depressive disorder (MDD) is a chronic, recurrent mental disease that causes serious disability. Because currently available antidepressants have limited efficacy with respect to response and remission in patients with MDD, clinicians must choose the best available treatment interventions for patients who do not respond to initial antidepressant treatment. The existing literature demonstrates that augmentation with atypical antipsychotics (AAs) shows higher response and remission rates compared with antidepressant monotherapy, but is associated with more withdrawals due to adverse events. In this paper, specific clinical issues in the use of AA augmentation for patients with MDD are briefly discussed. Given the limited information and clinical knowledge on the proper and effective use of AAs for MDD, future research should focus on practical clinical issues that can be commonly seen in routine practice but have not been addressed yet. This is because the use of AAs is likely to expand as there is good evidence for their effectiveness and tolerability as augmentation therapy for patients with MDD.

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Section: Clinical Issues In the Use Of Atypical Antipsychotics In CLImentioning

confidence: 99%

Clinical Issues in Use of Atypical Antipsychotics for Depressed Patients

Pae

Patkar

2013

CNS Drugs

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“…When a prodrug like codeine is administered to UMs they may suffer of adverse effects due to higher-than-expected concentrations of active metabolite morphine (148,149). Mutations in CYP2D6 gene can also alter substrate specifi city (150).…”

Section: Cyp2d6mentioning

confidence: 99%

Genetic Polymorphism of Metabolic Enzymes P450 (CYP) as a Susceptibility Factor for Drug Response, Toxicity, and Cancer Risk

Božina¹,

Bradamante

Lovrić

2009

Archives of Industrial Hygiene and Toxicology

166

111

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The polymorphic P450 (CYP) enzyme superfamily is the most important system involved in the biotransformation of many endogenous and exogenous substances including drugs, toxins, and carcinogens. Genotyping for CYP polymorphisms provides important genetic information that help to understand the effects of xenobiotics on human body. For drug metabolism, the most important polymorphisms are those of the genes coding for CYP2C9, CYP2C19, CYP2D6, and CYP3A4/5, which can result in therapeutic failure or severe adverse reactions. Genes coding for CYP1A1, CYP1A2, CYP1B1, and CYP2E1 are among the most responsible for the biotransformation of chemicals, especially for the metabolic activation of pre-carcinogens. There is evidence of association between gene polymorphism and cancer susceptibility. Pathways of carcinogen metabolism are complex, and are mediated by activities of multiple genes, while single genes have a limited impact on cancer risk. Multigenic approach in addition to environmental determinants in large sample studies is crucial for a reliable evaluation of any moderate gene effect. This article brings a review of current knowledge on the relations between the polymorphisms of some CYPs and drug activity/toxicity and cancer risk.

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“…72 The pooled OR of all Asians 12,[43][44][45] and available data in the subgroup of smokers 43,45 did not result in a large or significant OR. There was no evidence of heterogeneity or publication bias.…”

Section: Cyp1a2mentioning

confidence: 99%

Antipsychotic-induced tardive dyskinesia and polymorphic variations in COMT, DRD2, CYP1A2 and MnSOD genes: a meta-analysis of pharmacogenetic interactions

Bakker¹,

Harten²,

2008

Mol Psychiatry

138

118

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Despite accumulating evidence pointing to a genetic basis for tardive dyskinesia, results to date have been inconsistent owing to limited statistical power and limitations in molecular genetic methodology. A Medline, EMBASE and PsychINFO search for literature published between 1976 and June 2007 was performed, yielding 20 studies from which data were extracted for calculation of pooled estimates using meta-analytic techniques. Evidence from pooled data for genetic association with tardive dyskinesia (TD) showed (1) in COMT val158met , using Val-Val homozygotes as reference category, a protective effect for Val-Met heterozygotes (OR = 0.63, 95% CI: 0.46-0.86, P = 0.004) and Met carriers (OR = 0.66, 95% CI: 0.49-0.88, P = 0.005); (2) in Taq1A in DRD2, using the A1 variant as reference category, a risk-increasing effect for the A2 variant (OR = 1.30, 95% CI: 1.03-1.65, P = 0.026), and A2-A2 homozygotes using A1-A1 as reference category (OR = 1.80, 95% CI: 1.03-3.15, P = 0.037); (3) in MnSOD Ala9Val, using Ala-Ala homozygotes as reference category, a protective effect for Ala-Val (OR = 0.37, 95% CI: 0.17-0.79, P = 0.009) and for Val carriers (OR = 0.49, 95% CI: 0.24-1.00, P = 0.047). These analyses suggest multiple genetic influences on TD, indicative of pharmacogenetic interactions. Although associations are small, the effects underlying them may be subject to interactions with other loci that, when identified, may have acceptable predictive power. Future genetic research will take advantage of new genomic knowledge.

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

Cited by 152 publications

References 31 publications

Clinical Issues in Use of Atypical Antipsychotics for Depressed Patients

Clinical Issues in Use of Atypical Antipsychotics for Depressed Patients

Genetic Polymorphism of Metabolic Enzymes P450 (CYP) as a Susceptibility Factor for Drug Response, Toxicity, and Cancer Risk

Antipsychotic-induced tardive dyskinesia and polymorphic variations in COMT, DRD2, CYP1A2 and MnSOD genes: a meta-analysis of pharmacogenetic interactions

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