Abstract：
:Cytochrome P450 (CYP) 2D6 is one of the most important enzymes involved in the metabolism of drugs. Multiple, clinically relevant, genetic variants of this gene have been identified and, among them, a gene deletion as well as multiplications of the gene. These large structural mutations in CYP2D6 occur at a relatively high frequency in several populations. Genotyping of CYP2D6 could therefore be applied to individualize drug therapy to improve therapeutic efficacy and decrease adverse effects in patients. However, a prerequisite for the pharmacogenetic screening of CYP2D6 in a clinical setting is the development of fast, reliable and cost-effective techniques for the routine genotyping of patients. In the case of CYP2D6, besides the general problems that arise in the detection of large gene deletions and multiplications, the presence of two highly homologous pseudogenes, CYP2D7 and CYP2D8, forms an extra challenge. This review provides an overview of the techniques that have been described to detect the CYP2D6 gene deletion and multiplication: Southern-blotting RFLP, long-template PCR, and real-time PCR. Of these techniques, real-time PCR is the only technique giving quantitative information about the exact copy number of the gene. Considering all of the other advantages of this method over other methods, such as cost-effectiveness and suitability for high throughput screening, real-time PCR is the most promising method for the genotyping of large structural alterations in the CYP2D6 gene in a routine clinical setting.
journal_name
Drug Metab Revjournal_title
Drug metabolism reviewsauthors
Meijerman I,Sanderson LM,Smits PH,Beijnen JH,Schellens JHdoi
10.1080/03602530600952206subject
Has Abstractpub_date
2007-01-01 00:00:00pages
45-60issue
1eissn
0360-2532issn
1097-9883pii
770420517journal_volume
39pub_type
杂志文章,评审abstract：:Human cytochrome P450 (CYP) 3A subfamily members (mainly CYP3A4 and CYP3A5) mediate the metabolism of approximately half all marketed drugs and thus play a critical role in the drug metabolism. A huge number of studies on CYP3A-mediated drug metabolism in humans have demonstrated that CYP3A activity exhibits marked et...
journal_title：Drug metabolism reviews
pub_type： 杂志文章,评审
doi：10.1080/03602530701690374
更新日期：2007-01-01 00:00:00
abstract：:In summary, the concerns that environmental and other agents are causing adverse effects on reproductive function in humans are real, although the risk is not necessarily well characterized. The range of concerns for the types of effect that agents might have on reproduction span the full range of reproductive events....
journal_title：Drug metabolism reviews
pub_type： 杂志文章,评审
doi：10.3109/03602539608993992
更新日期：1996-02-01 00:00:00
abstract：:Drug transporters and drug metabolism enzymes govern drug absorption, distribution, metabolism and elimination. Many literature works presenting important aspects related to stereochemistry of drug metabolism are available. However, there is very little literature on stereoselectivity of chiral drug transport and enan...
journal_title：Drug metabolism reviews
pub_type： 杂志文章,评审
doi：10.3109/03602532.2014.887094
更新日期：2014-08-01 00:00:00
abstract：:The lung, which is in intimate contact with the external environment, is exposed to a number of toxicants both by virtue of its large surface area and because it receives 100% of the cardiac output. Lung diseases are a major disease entity in the U.S. population ranking third in terms of morbidity and mortality. Despi...
journal_title：Drug metabolism reviews
pub_type： 杂志文章,评审
doi：10.1081/dmr-120015694
更新日期：2002-11-01 00:00:00
abstract：:Enormous efforts toward predicting the metabolic fate of a drug have been driven by the high attrition rate in drug development. To accelerate such efforts, it is critical to elucidate the molecular mechanisms of drug recognition by drug-metabolizing enzymes. Therefore, it is not surprising that an increasing number o...
journal_title：Drug metabolism reviews
pub_type： 杂志文章,评审
doi：10.3109/03602532.2011.645581
更新日期：2012-02-01 00:00:00
abstract：:When target organ toxicity arises in animal models during routine drug safety evaluation, it raises several key questions: Is this target organ toxicity related to the pharmacology? What is the mode of action (MOA)? Is the target organ toxicity relevant to humans? Pathology or prior knowledge of the compound class may...
journal_title：Drug metabolism reviews
pub_type： 杂志文章,评审
doi：10.1081/dmr-120026395
更新日期：2003-11-01 00:00:00
abstract：:The aim of this study was to evaluate diazepam and oxazepam as cytochrome P450 inducers at doses previously shown to cause liver tumors in mice but not rats. In rats, diazepam and oxazepam induced CYP2B, and were as effective as phenobarbital despite lacking phenobarbital's tumor-promoting effect in rats. In mice, dia...
journal_title：Drug metabolism reviews
pub_type： 杂志文章
doi：10.1080/03602530600570081
更新日期：2006-01-01 00:00:00
abstract：:Aryl and heterocyclic amines are of particular interest because of their carcinogenicity. The N-hydroxy derivatives are formed by oxidation, usually by the cytochrome P450 (P450) enzymes and most often by P450 family 1. The mechanism of oxidation appears to resemble that of other P450 reactions. The N-hydroxy products...
journal_title：Drug metabolism reviews
pub_type： 杂志文章,评审
doi：10.1081/dmr-120005663
更新日期：2002-08-01 00:00:00
abstract：:Flavin-containing monooxygenases (FMOs) are important oxidative drug metabolizing enzymes. FMO3 is the primary human adult liver FMO enzyme, but is developmentally regulated. FMO3 promoter characterization using in vitro DNA binding assays with HepG2 cell and fetal and adult liver nuclear protein, as well as FMO3/repo...
journal_title：Drug metabolism reviews
pub_type： 杂志文章
doi：10.1080/03602530701498612
更新日期：2007-01-01 00:00:00
abstract：:At present, the methods and enzymology of the UDP-glucuronosyltransferases (UGTs) lag behind that of the cytochromes P450 (CYPs). About 15 human UGTs have been identified, and knowledge about their regulation, substrate selectivity, and tissue distribution has progressed recently. Alamethicin has been characterized as...
journal_title：Drug metabolism reviews
pub_type： 杂志文章,评审
doi：10.1081/dmr-120000653
更新日期：2001-08-01 00:00:00
abstract：:The cannabinoid receptor 1 (CB1) is a G protein-coupled receptor (GPCR) that is located primarily in the central nervous system. CB1 is a therapeutic target which may impact pathways to mediate pain, neurodegenerative disorders, hunger, and drug-seeking behavior. Despite these benefits, development of orthosteric ther...
journal_title：Drug metabolism reviews
pub_type： 杂志文章,评审
doi：10.1080/03602532.2018.1428342
更新日期：2018-02-01 00:00:00
abstract：:This article reviews the regulatory, social, policy, and other issues that will shape the development of pharmacogenomics applications. We identify and analyze 19 key public policy issues, ranging from the economic incentives for linked diagnostic-drug development, to the regulation of tests and drugs, and to privacy ...
journal_title：Drug metabolism reviews
pub_type： 杂志文章,评审
doi：10.1080/03602530801952500
更新日期：2008-01-01 00:00:00
abstract：:The multiple functions of NAD(P)H:quinone oxidoreductase 1 (NQO1, DT-diaphorase) in the cell are reviewed. NQO1 has long been viewed as a chemoprotective enzyme involved in cellular defense against the electrophilic and oxidizing metabolites of xenobiotic quinones. It also participates in reduction of endogenous quino...
journal_title：Drug metabolism reviews
pub_type： 杂志文章,评审
doi：10.1081/dmr-200033465
更新日期：2004-10-01 00:00:00
abstract：:The efficacy of drugs has to be demonstrated following the principal approach of statistical evaluation in controlled clinical trials. This scientifically and internationally accepted numerical approach has developed over the years to its importance, in contrast to the more pharmacologically attempt to extrapolate hum...
journal_title：Drug metabolism reviews
pub_type： 杂志文章,评审
doi：10.1081/dmr-200033500
更新日期：2004-10-01 00:00:00
abstract：:The mitochondrial amidoxime-reducing component (mARC) is a recently discovered molybdenum-containing enzyme in mammalians. Upon reconstitution with the electron transport proteins, cytochrome b(5) and its reductase, this molybdenum enzyme is capable of reducing N-hydroxylated compounds. It was named mARC because the N...
journal_title：Drug metabolism reviews
pub_type： 杂志文章,评审
doi：10.3109/03602532.2011.608682
更新日期：2011-11-01 00:00:00
abstract：:The cytochrome P450 (P450) field came out of interest in the metabolism of drugs, carcinogens, and steroids, which remain major focal points. Over the years we have come to understand the P450 system components, the multiplicity of P450s, and many aspects of the regulation of the genes and also the catalytic mechanism...
journal_title：Drug metabolism reviews
pub_type： 杂志文章,评审
doi：10.1081/dmr-120033996
更新日期：2004-05-01 00:00:00
abstract：:Hormone-dependent breast cancers that overexpress the ligand-binding nuclear transcription factor, estrogen receptor (ER), represent the most common form of breast epithelial malignancy. Exposure of breast epithelial cells to a redox-cycling and arylating quinone induces mitogen-activated protein kinase phosphorylatio...
journal_title：Drug metabolism reviews
pub_type： 杂志文章,评审
doi：10.1080/03602530600959391
更新日期：2006-01-01 00:00:00
abstract：:The present paper has discussed available test systems for determination of the response of G-6-PD-deficient human erythrocytes to environmental agents. The limitations and advantages of each model have been examined, and the results of research using each model have been presented. The future development of suitable ...
journal_title：Drug metabolism reviews
pub_type： 杂志文章,评审
doi：10.3109/03602538608998292
更新日期：1986-01-01 00:00:00
abstract：:Cytochrome P450 2D6 (CYP2D6) is a polymorphic enzyme responsible for metabolizing approximately 25% of all drugs. CYP2D6 is highly expressed in the brain and plays a role as the major CYP in the metabolism of numerous brain-penetrant drugs, including antipsychotics and antidepressants. CYP2D6 activity and inhibition h...
journal_title：Drug metabolism reviews
pub_type： 杂志文章,评审
doi：10.3109/03602532.2015.1047026
更新日期：2015-08-01 00:00:00
abstract：:Dehydroepiandrosterone has been thought to have physiological functions other than as an androgen precursor. The previous studies performed have demonstrated a number of biological effects in rodents, such as amelioration of disease in diabetic, chemical carcinogenesis, and obesity models. To date, activation of the p...
journal_title：Drug metabolism reviews
pub_type： 杂志文章,评审
doi：10.1080/03602530600569877
更新日期：2006-01-01 00:00:00
abstract：:Bioconjugation of therapeutic agents has been used as a selective drug delivery platform for many therapeutic areas. Bioconjugates are prepared by the covalent linkage of active compounds (small or large molecule) to a carrier molecule (lipids, proteins, peptides, carbohydrates, and polymers) through a chemical linker...
journal_title：Drug metabolism reviews
pub_type： 杂志文章,评审
doi：10.1080/03602532.2020.1716784
更新日期：2020-02-01 00:00:00
abstract：:Monkeys, especially macaques, including cynomolgus (Macaca fascicularis) and rhesus monkeys (Macaca mulatta), are frequently used in drug metabolism studies due to their evolutionary closeness to humans. Recently, numerous cytochrome P450 (P450 or CYP) cDNAs have been identified and characterized in cynomolgus and rhe...
journal_title：Drug metabolism reviews
pub_type： 杂志文章,评审
doi：10.3109/03602532.2010.549492
更新日期：2011-08-01 00:00:00
abstract：:The physiological and biochemical measurements that can be performed noninvasively in humans with modern imaging techniques offer great promise for defining the precise state of a patient's disease and its response to therapy. In general, there are two critical points in drug development when PET measurements are like...
journal_title：Drug metabolism reviews
pub_type： 杂志文章,评审
doi：10.3109/03602539709002238
更新日期：1997-11-01 00:00:00
abstract：:An association between marijuana use and schizophrenia has been noted for decades, and the recent emergence of high-efficacy synthetic cannabinoids (SCBs) as drugs of abuse has lead to a growing number of clinical reports of persistent psychotic effects in users of these substances. The mechanisms underlying SCB-elici...
journal_title：Drug metabolism reviews
pub_type： 杂志文章,评审
doi：10.1080/03602532.2018.1428343
更新日期：2018-02-01 00:00:00
abstract：:N-acetyltransferase 1 (NAT1), a polymorphic Phase II enzyme, plays an essential role in metabolizing heterocyclic and aromatic amines, which are implicated in urinary bladder cancer (BCa). This systematic review investigates a possible association between the different NAT1 genetic polymorphisms and BCa risk. Medline,...
journal_title：Drug metabolism reviews
pub_type： 杂志文章,meta分析,评审
doi：10.1080/03602532.2017.1415928
更新日期：2018-05-01 00:00:00
abstract：:By inhibiting ACE, captopril blocks the conversion of AI or AII and augments the effects of bradykinin both in vitro and in vivo. In rats, dogs, and monkeys with 2-kidney renal hypertension, orally administered captopril rapidly and markedly reduces blood pressure; this antihypertensive effect apparently occurs via a ...
journal_title：Drug metabolism reviews
pub_type： 杂志文章,评审
doi：10.3109/03602538409041080
更新日期：1984-01-01 00:00:00
abstract：:Atrial fibrillation (AF) is the most common arrhythmia in clinical practice and is associated with decreased quality of life, and increased mortality and morbidity from stroke and thromboembolism. The underlying mechanisms involved in the development of AF have yet to be fully elucidated. However, once initiated, AF t...
journal_title：Drug metabolism reviews
pub_type： 杂志文章,评审
doi：10.3109/03602532.2015.1077858
更新日期：2015-08-01 00:00:00
abstract：:A number of therapeutic drugs with different structures and mechanisms of action have been reported to undergo metabolic activation by Phase I or Phase II drug-metabolizing enzymes. The bioactivation gives rise to reactive metabolites/intermediates, which readily confer covalent binding to various target proteins by n...
journal_title：Drug metabolism reviews
pub_type： 杂志文章,评审
doi：10.1081/dmr-200028812
更新日期：2005-01-01 00:00:00
abstract：:The body is considered as a system composed of a number of subsystems. The response(s) of a drug is a complicated function of the concentration in the blood plasma, which in turn is some function of the dosage input. The dose-response curve of a drug in a subsystem (e.g., isolated organ) is, over a limited concentrati...
journal_title：Drug metabolism reviews
pub_type： 杂志文章,评审
doi：10.3109/03602538409015072
更新日期：1984-01-01 00:00:00
abstract：:Traditional Chinese medicine (TCM) has a long history of medical use in China and is still used worldwide. Unexpected herb-drug interactions (HDIs) may lead to adverse drug reactions or loss of therapeutic efficacy of the victim drug. Here, based on searches of Medline, EBSCO, Science Direct and Web of Science using v...
journal_title：Drug metabolism reviews
pub_type： 杂志文章,评审
doi：10.3109/03602532.2015.1124888
更新日期：2016-01-01 00:00:00
