Abstract:
:The Pharmacogenetics and Pharmacogenomics Knowledge Base (PharmGKB: http://www.pharmgkb.org) is devoted to disseminating primary data and knowledge in pharmacogenetics and pharmacogenomics. We are annotating the genes that are most important for drug response and present this information in the form of Very Important Pharmacogene (VIP) summaries, pathway diagrams, and curated literature. The PharmGKB currently contains information on over 500 drugs, 500 diseases, and 700 genes with genotyped variants. New features focus on capturing the phenotypic consequences of individual genetic variants. These features link variant genotypes to phenotypes, increase the breadth of pharmacogenomics literature curated, and visualize single-nucleotide polymorphisms on a gene's three-dimensional protein structure.
journal_name
Drug Metab Revjournal_title
Drug metabolism reviewsauthors
Sangkuhl K,Berlin DS,Altman RB,Klein TEdoi
10.1080/03602530802413338subject
Has Abstractpub_date
2008-01-01 00:00:00pages
539-51issue
4eissn
0360-2532issn
1097-9883pii
904746277journal_volume
40pub_type
杂志文章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::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::Voriconazole, a second-generation triazole frequently used for the prophylaxis and treatment of invasive fungal infections, undergoes complex metabolism mainly involving various (polymorphic) cytochrome P450 enzymes in humans. Although high inter- and intraindividual variability in voriconazole pharmacokinetics have b...
journal_title:Drug metabolism reviews
pub_type: 杂志文章,评审
doi:10.1080/03602532.2019.1632888
更新日期:2019-08-01 00:00:00
abstract::In this paper, we evaluate methodologies and null mouse models used to study drug transporter function in vitro and in vivo. P-glycoprotein and MRP null mice have been used to examine many aspects of xenobiotic distribution and bioavailability. Their advantage over conventional models is that they allow the exclusion ...
journal_title:Drug metabolism reviews
pub_type: 杂志文章,评审
doi:10.1080/03602530802605040
更新日期:2009-01-01 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::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::Herbert Remmer was a pioneer in the study of the phenomenon of enzyme induction. He was also a leading figure, if not the foremost, in the development of the discipline of toxicology in Germany during his tenure as Professor of Toxicology at the University of Tübingen. Included here are some brief thoughts about where...
journal_title:Drug metabolism reviews
pub_type: 传,历史文章,杂志文章
doi:10.1081/dmr-200033409
更新日期:2004-10-01 00:00:00
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...
journal_title:Drug metabolism reviews
pub_type: 杂志文章,评审
doi:10.1080/03602530600952206
更新日期:2007-01-01 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::Much is known about the distal DNA damage repair response. In particular, many of the enzymes and auxiliary proteins that participate in DNA repair have been characterized. In addition, knowledge of signaling pathways activated in response to DNA damage is increasing. In contrast, comparatively less is known of DNA da...
journal_title:Drug metabolism reviews
pub_type: 杂志文章,评审
doi:10.1080/03602530600959649
更新日期:2006-01-01 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 CYP4 family of cytochrome P450 enzymes and the mammalian peroxidases covalently bind their heme groups. In the CYP4 enzymes this involves one, and in the peroxidases two, covalent ester links between heme methys and carboxylic acid side-chains. In addition, in myeloperoxidase, a methionine forms a sulfonium link t...
journal_title:Drug metabolism reviews
pub_type: 杂志文章,评审
doi:10.1080/03602530802186439
更新日期:2008-01-01 00:00:00
abstract::Population pharmacokinetics describe the typical relationships between physiology (both normal and disease altered) and pharmacokinetics, the interindividual variability in these relationships, and their residual intraindividual variability. Knowledge of population kinetics can help one to choose initial drug dosage, ...
journal_title:Drug metabolism reviews
pub_type: 杂志文章
doi:10.3109/03602538409015063
更新日期:1984-01-01 00:00:00
abstract::Human CYP1A2 is one of the major CYPs in human liver and metabolizes a number of clinical drugs (e.g., clozapine, tacrine, tizanidine, and theophylline; n > 110), a number of procarcinogens (e.g., benzo[a]pyrene and aromatic amines), and several important endogenous compounds (e.g., steroids). CYP1A2 is subject to rev...
journal_title:Drug metabolism reviews
pub_type: 杂志文章,评审
doi:10.3109/03602530903286476
更新日期:2010-05-01 00:00:00
abstract::Mineral fibers, including asbestos, are ubiquitous contaminants of the environment. Asbestos fibers are generally present at levels below 1 fiber/L in air though 10 fibers/L may be found in cities; these levels do not appear to be high enough to present a hazard to health. These fibers come mostly from the use of fibr...
journal_title:Drug metabolism reviews
pub_type: 杂志文章,评审
doi:10.3109/03602539408998321
更新日期:1994-01-01 00:00:00
abstract::Chemicals that cause toxicity though a direct mechanism, such as acetaminophen, covalently bind to a select group of proteins prior to the development of toxicity, and these proteins may be important in the initiation of the events that lead to the hepatotoxicity. Disruption of the cell is measured by release of intra...
journal_title:Drug metabolism reviews
pub_type: 杂志文章,评审
doi:10.3109/03602539709037572
更新日期:1997-02-01 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::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 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
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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::Ronald Estabrook made his initial impact studying cytochrome P450 by demonstrating the oxidative metabolism function of this unique class of enzymes, which had an unusual spectral peak at 450 nm when reduced and in the presence of carbon monoxide. Utilizing a photochemical action spectrum, he demonstrated that a cytoc...
journal_title:Drug metabolism reviews
pub_type: 传,历史文章,杂志文章
doi:10.1080/03602530701468318
更新日期:2007-01-01 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::Like any other drugs, antiallergic medications can be associated with large inter- and intraindividual variability in their disposition. The best-documented examples belong to the H1 antihistamines. Variable drugs are more likely to show unpredictable therapeutic response with both increased risks of side effects and ...
journal_title:Drug metabolism reviews
pub_type: 杂志文章,评审
doi:10.1080/10837450902891485
更新日期:2009-01-01 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::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::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::Hyperbilirubinemia may accompany harmful effects such as jaundice, brain dysfunction, and pharmacokinetic alterations of drugs. Clinical drugs are the important causes of hyperbilirubinemia, especially for patients with certain pathologic conditions or with genetic variations. This article reviews hyperbilirubinemic p...
journal_title:Drug metabolism reviews
pub_type: 杂志文章,评审
doi:10.1080/03602530802341133
更新日期:2008-01-01 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::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::Global statistical data shed light on an alarming trend that every year thousands of people die due to adverse drug reactions as each individual responds in a different way to the same drug. Pharmacogenomics has come up as a promising field in drug development and clinical medication in the past few decades. It has em...
journal_title:Drug metabolism reviews
pub_type: 杂志文章,评审
doi:10.3109/03602532.2015.1047027
更新日期:2015-08-01 00:00:00