Frequency of CYP2D6*10 and *14 Alleles and their Influence on the Metabolic Activity of CYP2D6 in a Healthy Chinese Population

Cai, Wei; Chen, B; Zhang, W X

doi:10.1038/sj.clpt.6100015

Cited by 27 publications

(30 citation statements)

References 13 publications

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“…These allele frequencies are similar to those that have been reported in other Asian populations but higher than those reported for Caucasians and African Americans, in whom the frequency of the CYP2D6*10 allele was found to be 2%-5% [9,10] . In Japanese psychiatric patients, the number of CYP2D6*10 alleles has been found to significantly affect dose-corrected plasma risperidone levels [18] .…”

Section: Discussionsupporting

confidence: 70%

“…Additionally, CYP2D6 polymorphisms (*10, *5) affect the pharmacokinetic parameters of other atypical antipsychotic drugs, such as risperidone [8] and aripiprazole [9] . The allele frequencies of CYP2D6*10 (rs1065852, allele C>T) mutations are 48%-70% [10] and 30%-50% [11] in Chinese and other Asian populations (eg, Japanese and Korean populations), respectively. However, the effects of the CYP2D6*10 (rs1065852) mutation on the pharmacokinetics of iloperidone in clinical practice remain unknown.…”

Section: Original Articlementioning

confidence: 99%

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Influences of CYP2D6*10 polymorphisms on the pharmacokinetics of iloperidone and its metabolites in Chinese patients with schizophrenia: a population pharmacokinetic analysis

Pei

Huang

et al. 2016

Acta Pharmacol Sin

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Aim: Iloperidone is an atypical antipsychotic drug that is mainly metabolized by CYP2D6, CYP3A4, and cytosolic enzymes. Previous studies show that extensive and poor metabolizers of CYP2D6 exhibit different plasma concentrations of iloperidone and its metabolites. The aim of this study was to develop a parent-metabolite population pharmacokinetic (PPK) model to quantify the effects of CYP2D6*10 allele on the pharmacokinetics of iloperidone and its metabolites in Chinese schizophrenia patients. Methods: Seventy Chinese schizophrenia patients were enrolled, from whom limited blood samples were collected on d 15 (0 h) and d 28 (0, 4 and 12 h after drug administration). The plasma concentrations of iloperidone and its metabolites M 1 (P-88) and M 2 (P-95) were simultaneously detected using a validated HPLC-MS assay. CYP2D6*10 (rs1065852) genotyping was performed. A PPK model was developed based on data from the patients using the NONMEM software (version 7.2). A one-compartment model with first-order absorption and elimination was used to describe the pharmacokinetic data related to iloperidone and its metabolites. Results: Patients with the CYP2D6*10 T/T genotype had significantly higher concentrations of iloperidone and M 1 , and lower concentrations of M 2 than the patients with C/C or C/T genotypes. The CYP2D6*10 genotype affected the elimination constants for transformation of iloperidone to the metabolites M 1 (K 23 ) and M 2 (K 24 ). The K 23 value of the patients with T/T genotype was 1.34-fold as great as that of the patients with C/C or C/T genotype. The K 24 value of the patients with C/T and T/T genotypes was 0.693-and 0.492-fold, respectively, as low as that of the patients with C/C genotype. Conclusion: CYP2D6*10 mutations affect the pharmacokinetics of iloperidone and its metabolites in Chinese schizophrenia patients, suggesting that the clinical doses of iloperidone for patients with CYP2D6*10 mutations need to be optimized.

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Section: Discussionsupporting

confidence: 70%

Section: Original Articlementioning

confidence: 99%

Influences of CYP2D6*10 polymorphisms on the pharmacokinetics of iloperidone and its metabolites in Chinese patients with schizophrenia: a population pharmacokinetic analysis

Pei

Huang

et al. 2016

Acta Pharmacol Sin

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“…It is an important enzyme responsible for the metabolism of 25% of drugs, including antipsychotics and antidepressants. It is polymorphically expressed, being absent in 6-10% of Caucasians and 1% of Asians, 1 who are known as poor metabolizers (PMs). Patients with two wild-type (wt) or functional alleles are referred to as extensive metabolizers (EMs).…”

Section: Introductionmentioning

confidence: 99%

Cytochrome P450 testing for prescribing antipsychotics in adults with schizophrenia: systematic review and meta-analyses

et al. 2010

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There is wide variability in the response of individuals to standard doses of antipsychotic drugs. It has been suggested that this may be partly explained by differences in the cytochrome P450 (CYP450) enzyme system responsible for metabolizing the drugs. We conducted a systematic review and metaanalyses to consider whether testing for CYP450 single nucleotide polymorphisms in adults starting antipsychotic treatment for schizophrenia predicts and leads to improvements in clinical outcomes. High analytic validity in terms of sensitivity and specificity was seen in studies reporting P450 testing. However, there was limited evidence of the role of CYP2D6 polymorphisms in antipsychotic efficacy, although there was an association between CYP2D6 genotype and extrapyramidal adverse effects. No studies reported on the prospective use of CYP2D6 genotyping tests in clinical practice. In conclusion, evidence of clinical validity and utility of CYP2D6 testing in patients being prescribed antipsychotics is lacking, and thus, routine pharmacogenetic testing prior to antipsychotic prescription cannot be supported at present. Further research is required to improve the evidence base and to generate data on clinical validity and clinical utility.

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“…For example, a number of studies have found that around 7% of Caucasians are PMs compared with 1% of Asians, with data for other ethnic groups less cogent. 21 However, fewer Asians metabolise CYP2D6 normally, largely because of high frequencies of the *10 allele, 22 resulting in a 24 a Some studies make no distinction between EMs and IMs whereas others classify these as homozygous EMs and heterozygous EMs respectively (but not all heterozygous EMs will necessary be IMs). Similarly, not all studies make distinctions with ultrarapid metabolisers (and not all pharmacogenetic tests are capable of detecting patients with multiple copies of alleles and thus making this distinction).…”

Section: *41x2mentioning

confidence: 99%

“…This decreased activity allele, which is rare in Caucasian populations, has been estimated to be as high as 55% in Chinese populations. 21,23 The classification used in Table 3 is the one that is used by the first approved pharmacogenetic test, the AmpliChip. This test also tests for CYP2C19 and patients are given either an extensive metaboliser (EM) or a PM phenotype, reflecting the fact that the *1 allele is a normal activity allele whereas *2 and *3 are associated with loss of function.…”

Section: *41x2mentioning

confidence: 99%

The clinical effectiveness and cost-effectiveness of testing for cytochrome P450 polymorphisms in patients with schizophrenia treated with antipsychotics: a systematic review and economic evaluation

Fleeman

McLeod²,

Bagust³

et al. 2010

Health Technol Assess

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How to obtain copies of this and other HTA programme reports An electronic version of this title, in Adobe Acrobat format, is available for downloading free of charge for personal use from the HTA website (www.hta.ac.uk). A fully searchable DVD is also available (see below).Printed copies of HTA journal series issues cost £20 each (post and packing free in the UK) to both public and private sector purchasers from our despatch agents.Non-UK purchasers will have to pay a small fee for post and packing. For European countries the cost is £2 per issue and for the rest of the world £3 per issue. How to order:-fax (with credit card details) -post (with credit card details or cheque) -phone during office hours (credit card only).Additionally the HTA website allows you to either print out your order or download a blank order form. Contact details are as follows:Synergie UK (HTA Department) Digital House, The Loddon Centre Wade Road Basingstoke Hants RG24 8QW Email: orders@hta.ac.uk Tel: 0845 812 4000 -ask for 'HTA Payment Services' (out-of-hours answer-phone service) Fax: 0845 812 4001 -put 'HTA Order' on the fax header Payment methods Paying by chequeIf you pay by cheque, the cheque must be in pounds sterling, made payable to University of Southampton and drawn on a bank with a UK address. Paying by credit cardYou can order using your credit card by phone, fax or post. SubscriptionsNHS libraries can subscribe free of charge. Public libraries can subscribe at a reduced cost of £100 for each volume (normally comprising 40-50 titles). The commercial subscription rate is £400 per volume (addresses within the UK) and £600 per volume (addresses outside the UK). Please see our website for details. Subscriptions can be purchased only for the current or forthcoming volume. How do I get a copy of HTA on DVD?Please use the form on the HTA website (www.hta.ac.uk/htacd/index.shtml). HTA on DVD is currently free of charge worldwide.The website also provides information about the HTA programme and lists the membership of the various committees. HTA NIHR Health Technology Assessment programmeT he Health Technology Assessment (HTA) programme, part of the National Institute for Health Research (NIHR), was set up in 1993. It produces high-quality research information on the effectiveness, costs and broader impact of health technologies for those who use, manage and provide care in the NHS. 'Health technologies' are broadly defined as all interventions used to promote health, prevent and treat disease, and improve rehabilitation and long-term care. The research findings from the HTA programme directly influence decision-making bodies such as the National Institute for Health and Clinical Excellence (NICE) and the National Screening Committee (NSC). HTA findings also help to improve the quality of clinical practice in the NHS indirectly in that they form a key component of the 'National Knowledge Service'. The HTA programme is needs led in that it fills gaps in the evidence needed by the NHS. There are three routes to the start of projec...

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Frequency of CYP2D610 and 14 Alleles and their Influence on the Metabolic Activity of CYP2D6 in a Healthy Chinese Population

Cited by 27 publications

References 13 publications

Influences of CYP2D6*10 polymorphisms on the pharmacokinetics of iloperidone and its metabolites in Chinese patients with schizophrenia: a population pharmacokinetic analysis

Influences of CYP2D6*10 polymorphisms on the pharmacokinetics of iloperidone and its metabolites in Chinese patients with schizophrenia: a population pharmacokinetic analysis

Cytochrome P450 testing for prescribing antipsychotics in adults with schizophrenia: systematic review and meta-analyses

The clinical effectiveness and cost-effectiveness of testing for cytochrome P450 polymorphisms in patients with schizophrenia treated with antipsychotics: a systematic review and economic evaluation

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