CYP2C9

..To assess the possible use of this reaction as an in vivo marker of CYP3A4 activity, we studied the involvement of cytochromes CYP2C9, CYP2E1 and CYP3A4 in the in vivo oxidative metabolism of quinidine.

..to warfarin therapy, we determined the frequency and functional effects of polymorphisms of the predominant cytochrome P450 subfamily responsible for warfarin metabolism (eg, CYP2C9) in an ethnically defined U.S. patient population.

..We determined DNA sequence variants in CYP2C9 and VKORC1 in 16 Chinese patients having warfarin sensitivity (< or = 1...

Several studies have linked mutations in the genes encoding cytochrome P450 2C9 (CYP2C9) and vitamin K epoxide reductase complex 1 (VKORC1) to a reduced warfarin dose requirement and an increased risk of bleeding with warfarin treatment, ..

The objective of this study was to study the effect of CYP2C9 genetic polymorphism and undernourishment on free phenytoin concentrations in epileptic patients...

..another approximately 12% by two non-synonymous SNPs (*2, *3) in the cytochrome P450 warfarin-metabolizing gene CYP2C9. We initially tested each of 325,997 GWAS SNPs for association with warfarin dose by univariate regression and ..

The objective of this study was to assess the contribution of the VKORC1 and CYP2C9 genotypes and age, body size, and weight of the patients to the warfarin dose requirement in a Chinese population.

..four genes, vitamin K epoxide reductase (VKORC1), gamma-glutamyl carboxylase (GGCX), calumenin (CALU), and cytochrome P450 2C9 (CYP2C9) to the warfarin maintenance dose required in Japanese patients following ischemic stroke...

..0 x 10(-123)). The lowest P-value on chromosome 10 was obtained by rs4086116 within cytochrome P450 2C9 (CYP2C9) (P = 3.3 x 10(-24))...

..Numerous papers have shown the important contribution of CYP2C9 and VKORC1 genetic variants to this variability...

..Human CYP450 proteins CYP1A2, CYP2C9, CYP2C19, CYP2D6 and CYP3A4 are the major drug-metabolizing isoforms, and contribute to the oxidative metabolism ..

..In our study, polymorphisms in or flanking the genes VKORC1, CYP2C9, CYP2C18, CYP2C19, PROC, APOE, EPHX1, CALU, GGCX and ORM1-ORM2 and haplotypes of VKORC1, CYP2C9, CYP2C8, CYP2C19, ..

..Pharmacogenetic-guided dosing of warfarin is a promising application of "personalized medicine" but has not been adequately tested in randomized trials...

Cytochrome P450 (CYP) 2C9 is an important enzyme involved in xenobiotics metabolism. This study investigated the association of CYP2C9 gene coding region polymorphisms with colorectal cancer (CRC) in Chinese Han population.

Warfarin, a widely prescribed oral anticoagulant, is used for the prevention of thromboembolism. Polymorphisms in CYP2C9 and VKORC1 have been shown to be associated with warfarin dose requirements...

To search for the optimal dosage of phenytoin in patients with epilepsy based on the metabolic activities of CYP2C9 and CYP2C19 polymorphisms, a total of 169 patients receiving phenytoin treatment for more than 1 month were recruited...

..et al. (2004) Mol. Pharmacol. 65, 842-850] revealed some unusual properties of the R108H mutant of cytochrome P450 2C9 (CYP2C9), including elevated thermostability relative to that of CYP2C9, as well as a UV-visible absorbance ..

Accumulating evidence indicates that CYP2C9 ranks amongst the most important drug metabolizing enzymes in humans. Substrates for CYP2C9 include fluoxetine, losartan, phenytoin, tolbutamide, torsemide, S-warfarin, and numerous NSAIDs...

b>CYP2C9 polymorphisms are associated with decreased S-warfarin clearance and lower maintenance dosage. Decreased expression of VKORC1 resulting from the -1639G>A substitution has also been implicated in lower warfarin dose requirements...

Cytochrome P-450 (CYP) 2C9 CYP2C9 is a polymorphically expressed enzyme responsible for the metabolism of several clinically important drugs, some with a low therapeutic index...

The cytochrome P450 enzyme CYP2C9 catalyses the metabolism of numerous therapeutic agents, including the anti-epileptic drug phenytoin...

..differences in dose response can partially be explained by known genetic polymorphisms in the metabolic enzyme CYP2C9 but a large deal of individual variability remains still unexplained...

b>CYP2C9 is one of the major drug metabolizing enzymes for many drugs including warfarin, NSAIDs and losartan. It is polymorphic in many populations...

Warfarin dosing is correlated with polymorphisms in vitamin K epoxide reductase complex 1 (VKORC1) and the cytochrome P450 2C9 (CYP2C9) genes...

Phenytoin, a widely used anti-epileptic drug, is metabolized mainly by CYP2C9 (90%) and partly by CYP2C19 (10%) to its major metabolite 5-(para-hydroxyphenyl)-5- phenylhydantoin (p-HPPH)...

..Pharmacogenetics aims to maximize benefits and minimize risks of drug treatment. Our objectives were to examine the influence of common variants of hepatic metabolism and transporter genes on the lipid-lowering response to statin therapy...

..differ among racial groups, most pharmacogenetic algorithms for genotype-guided warfarin dosing only include two CYP2C9 alleles (*2 and *3) and a single VKORC1 allele (g.-1639G>A or g.1173C>T) commonly found among Caucasians...

The two published crystal structures of cytochrome P450 2C9, complexed with ( S)-warfarin or flurbiprofen, implicate a cluster of three active site phenylalanine residues (F100, F114, F476) in ligand binding...

..SNPs in the CYP2C9 gene have increasingly been recognized as determinants of the metabolic phenotype that underlies interindividual ..

..To address the association of genetic factors and warfarin dosage for ethnic Han Chinese, we genotyped six candidate genes involved in the warfarin interactive pathway with focus on SNPs with reported association with warfarin dose...

Genetic polymorphisms of CYP2C9 among different populations in different geographical regions could be different...

..The aim was to evaluate the influence of two CYP2C9 functional polymorphisms (*2 and *3) on warfarin dose in African-Americans, an unstudied population and Caucasians,..

To determine the frequencies of the variant alleles and the genotypes of CYP2C9 in a Korean population.

..Using polymerase chain reaction, we genotyped each participant for the presence of 8 polymorphisms in the cytochrome P450 2C9 system. Using multiple regression, we quantified the association between warfarin dose and all factors...

b>CYP2C9-dependent drug metabolism is subject to large interindividual variation. To some extent, this is explained by genetic polymorphism with expression of enzyme variants that differ in catalytic activity...

..using a global and a population pharmacokinetic model considering functionally relevant polymorphisms of CYP2B6, CYP2C9, CYP2C19, CYP3A5, and GSTA1...

..We conducted a retrospective cohort study to test whether genetic polymorphisms of these enzymes are associated with the toxicity of, and clinical response to, cyclophosphamide in patients with lupus nephritis...

..We investigated the predictive value of genetic variants of CYP2D6, CYP2C19, and three other cytochrome P450 enzymes for tamoxifen treatment outcome...

..5-hydroxylation, while, in vitro, the 4'-hydroxylation and 3'-hydroxylation seem to be mediated mainly by CYP2C9. We have demonstrated the relevance of CYP2C9 genotypes for diclofenac 4'-hydroxylation in healthy volunteers, so ..

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b>CYP2C9, CYP2C19, and CYP2D6 belong to a subfamily of cytochrome P450 (CYP) enzymes, associated mainly with the metabolism of exogenous compounds in the human body...

The aim of the study is to explore the contribution of genetic factors related either to drug metabolism (cytochrome P450 2C9) or to drug target (vitamin K epoxide reductase) to variability in the response to acenocoumarol among 222 ..

Our objective was to prospectively study the impact of CYP2C9 polymorphism (*2 and *3) on the risk of overanticoagulation during the induction phase of warfarin therapy.

..We performed a case-control study to determine the prevalence of epoxygenase-related SNP in African American individuals and to evaluate whether these SNP are associated with increased risk of hypertension...

Cytochrome P450 (CYP) superfamily members CYP2C8 and CYP2C9 are polymorphically expressed enzymes that are involved in the metabolic inactivation of several drugs, including, among others, antiepileptics, NSAIDs, oral hypoglycemics, and ..

..This study describes the relationship between genetic variants of CYP2C8 and CYP2C9, and morbidity in myocardial infarction in a large Swedish patient material...

Warfarin anticoagulation effect is characterized by marked variability, some of which has been attributed to CYP2C9 polymorphisms...

To study the effect of CYP2C8*3, the most common CYP2C8 variant allele on the dis-position of (R)-ibuprofen and the association of CYP2C8*3 with variant CYP2C9 alleles.

To assess whether CYP2C9 alleles other than CYP2C9*2 and *3 are associated with a low-warfarin dose requirement and the relevance of upstream CYP2C9 polymorphisms to dose requirement and metabolism.

..e., CYP2C9) and activity (i.e., vitamin K epoxide reductase complex subunit 1-VKORC1)...

Cytochrome P-450 2C9 (CYP2C9) polymorphisms (CYP2C9*2 and CYP2C9*3) reduce the clearance of warfarin, increase the risk of bleeding, and prolong the time to stable dosing...

..Reporter assays with a chimeric CYP2C9-LUC construct demonstrated that the sole transfection of coactivators induced luciferase activity in HepG2 cells...

..and pharmacodynamic factors associated with population differences in warfarin doses needed to achieve anticoagulation, in particular the possible involvement of genetic variability in vitamin K epoxide reductase (VKOR) and CYP2C9.

..Patients possessing variants (*2 and *3) of the cytochrome P450 2C9 gene require reduced maintenance doses compared to those having wild-type alleles (*1)...

..The aim of this study was to explore the frequencies of polymorphisms in drug-metabolizing enzymes (CYP1A1, CYP2C9, CYP2C19, CYP3A4, CYP2D6, CYP3A5, DPYD, UGT1A1, GSTM1, GSTP1, GSTT1) and drug transporters (ABCB1[MDR1] and ABCC2[..

..This study investigated the contribution of age, CYP2C9 and VKORC1 genotype, and body size to warfarin-dose requirements...

..Patients with either Cytochrome P-450 CYP2C9*2, CYP2C9*3, or VKORC1*2 genotype (c...

..To determine developmental expression patterns, liver microsomal CYP2C9 and -2C19 were measured (n = 237; ages, 8 weeks gestation-18 years) by Western blotting and with diclofenac or ..

..incidence of alleles CYP2C8*1 to *5 in a Spanish population; (ii) to test the impact of such alleles, and those of CYP2C9, on the metabolism of racemic ibuprofen, R-ibuprofen and S-ibuprofen; and (iii) to discern whether those metabolic ..

..The principal enzyme involved in warfarin metabolism is CYP2C9, and 2 relatively common variant forms with reduced activity have been identified, CYP2C9*2 and CYP2C9*3...

Although the influence of VKORC1 and CYP2C9 polymorphisms on warfarin response has been studied, variability in dose explained by CYP2C9 and VKORC1 is lower among African-Americans compared with European-Americans...

b>CYP2C9 is a major enzyme in human drug metabolism and the polymorphism observed in the corresponding gene may affect the therapeutic outcome during treatment with several drugs...

..dose required to achieve the desired anticoagulant response can only partly be explained by polymorphisms in the CYP2C9 gene, suggesting that additional genetic factors such as polymorphisms in genes involved in blood coagulation may ..

To determine the frequencies of CYP2C9 variants in the Korean population and compare them with the frequencies in other ethnic populations.

b>CYP2C9 and VKORC1 genotypes predict therapeutic warfarin dose at initiation of therapy; however, the predictive ability of genetic information after a week or longer is unknown...

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..nucleotide substitutions are known to result in a different amino acid at one of four sites in cytochrome P4502C9 (CYP2C9) namely: residue 144: Arg/Cys; residue 358: Tyr/Cys; residue 359: Ile/Leu and residue 417: Gly/Asp...

..Four members of this subfamily have been identified in humans: CYP2C8, CYP2C9, CYP2C18, and CYP2C19...

The objective of this study was to assess the relative influence of VKORC1 and CYP2C9 genetic variants on several clinical outcomes related to warfarin treatment...

Cytochrome P450 (CYP) 2C8 and 2C9 are polymorphic enzymes. The CYP2C8*3 and CYP2C9*2 are the major variant alleles in Caucasian populations...

To investigate the distribution of cytochrome P450 2C9 (CYP2C9) and 2C19 (CYP2C19) genotype frequencies in the Beninese and Belgian Caucasian populations.

..b>CYP2C9( *)2 (p.R144C), CYP2C9( *)3 (p.I359L), and the VKORC1 promoter (g...

The cytochrome P450 CYP2C9 is responsible for the metabolism of S-warfarin. Two known allelic variants CYP2C9*2 and CYP2C9*3 differ from the wild type CYP2C9*1 by a single aminoacid substitution in each case...

Genetic variants of the enzyme that metabolizes warfarin, cytochrome P-450 2C9 (CYP2C9), and of a key pharmacologic target of warfarin, vitamin K epoxide reductase (VKORC1), contribute to differences in patients' responses to various ..

..We developed and validated a warfarin-dosing algorithm for a multi-ethnic population that predicts the best dose for stable anticoagulation, and compared its performance against other regression equations...

..The purpose of this study was to evaluate the effects of known allelic variants in the CYP2B6, CYP2C9, CYP2C19, CYP3A4, CYP3A5, GSTA1, GSTP1, ALDH1A1 and ALDH3A1 genes on the pharmacokinetics of the anticancer agent, ..

This study analyzed the frequency of CYP2C9 variant alleles and evaluated the impact of CYP2C9 genotype on diclofenac metabolism in a Spanish population.

The cytochrome P450 enzyme CYP2C9 catalyses the 4'-hydroxylation of the nonsteroidal analgesic drug diclofenac in humans...

..To study the frequency distribution of cytochrome P450 (CYP) functional genetic variants in five Eurasian populations from the territory of Siberia in Russia...

..Warfarin is commonly prescribed for prophylaxis and treatment of thromboembolism after orthopedic surgery. During warfarin initiation, out-of-range International Normalized Ratio (INR) values and adverse events are common...

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT * Genetic polymorphisms of VKORC1 and CYP2C9 are known to influence warfarin dosage...

..b>CYP2C9 is almost exclusively responsible for the metabolism of the pharmacologically more active (S)-enantiomer...

..0 to 3.5, we analyzed the CYP2C9 (cytochrome P450 2C9) and VKORC1 (vitamin K epoxide reductase complex, subunit 1) genetic loci to study the relationship among ..

..Nilotinib has shown competitive inhibition of cytochrome P450 enzyme (CYP) 2C9 in vitro, but its effect on CYP2C9 activity in humans is unknown...

..To investigate the inhibition potential and kinetic information of noscapine to seven CYP isoforms and extrapolate in vivo noscapine-warfarin interaction magnitude from in vitro data...

..Variants of two genes, CYP2C9 and VKORC1, account for 30-50% of the variability in dosing of warfarin; thus, many believe that testing of these ..

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT * CYP2C9 single nucleotide polymorphisms (SNPs) are important in safe and effective oral anticoagulation with warfarin use...

..We hypothesized that hydroxywarfarins inhibit the hydroxylation of warfarin by CYP2C9, thereby limiting enzymatic capacity toward S-warfarin...

..Warfarin metabolism is under genetic control, involving primarily the CYP2C9 gene encoding the enzyme that catalyzes the conversion of warfarin to inactive metabolites.

..Genetic variability in the VKORC1 and CYP2C9 genes is associated with increased warfarin sensitivity...

..With regard to the metabolism of AEDs, the polymorphic CYP2C9 and CYP2C19 are of interest...

To investigate the impact of genetic polymorphisms in CYP2D6, CYP3A5, CYP2C9 and CYP2C19 on the pharmacokinetics of tamoxifen and its metabolites in Asian breast cancer patients.

The identification of the genes encoding CYP2C9, the principal metabolizing enzyme of the coumarins, and VKORC1, the molecular target for coumarins, has strongly stimulated the research on pharmacogenetics of vitamin K antagonists, also ..

..CYP2D6, CYP2C19 and CYP2C9 gene polymorphisms and gene duplications account for the most frequent variations in phase I metabolism of drugs ..

..CYP2C19, CYP2C8, CYP2C18, and CYP2C9 formed a single metabolite with an HPLC retention time identical to that of 5OH-OP...

..Progesterone catabolism occurs primarily in the liver via the cytochrome P450 2C (CYP2C) and cytochrome P450 3A (CYP3A) subfamilies (EC 1.14.14.1; unspecific monooxygenases)...

We have examined the kinetics of substrate metabolism by cDNA-expressed human CYP2C9 and the R144C variant...

..inbred strain of mice in which administration of polycyclic aromatic hydrocarbons (PAHs) does not induce microsomal monooxygenase activity...

..rates in a characterized microsomal bank correlated with the catalytic activities for cytochrome P450 (CYP) 2D6, CYP2C9, and CYP2C8...

..vitro investigation were 1) to compare the rate of celecoxib hydroxylation by different genetic variants of cytochrome P450 2C9 (CYP2C9), and 2) to identify the enzyme(s) involved in the formation of the major metabolite ..

..discussed the substrate specificity, inhibitor selectivity and structure-activity relationship (SAR) of human CYP2C9. The features of CYP2C9 pharmacophore and SAR models have been elaborated...

..In the previous funding period the focus was primarily on genetic variation within the cytochrome P450 enzyme, CYP2C9, because it controls metabolic clearance of the more potent (S) enantiomer of the racemic drug...

..Warfarin is metabolized by two distinct subfamilies of the cytochrome P450 complex: CYP2A6 and CYP2C9. Common polymorphisms of these enzymes result in impaired warfarin metabolism...

..In the previous funding period the focus was primarily on genetic variation within the cytochrome P450 enzyme, CYP2C9, because it controls metabolic clearance of the more potent (S) enantiomer of the racemic drug...

..by clinical factors including gender, age, body surface area, diabetes status, heart valves, concomitant use of CYP2C9 inducers, and genetic factors including CYP2C9 and VKORC1 genotype...

..by clinical factors including gender, age, body surface area, diabetes status, heart valves, concomitant use of CYP2C9 inducers, and genetic factors including CYP2C9 and VKORC1 genotype...

..that the rat is a valid model for the human condition because the highly publicized warfarin-interacting genes Cyp2c9 and Vkorc1 emerged from preliminary analyses. However, novel sex-specific effects were observed...

..that the rat is a valid model for the human condition because the highly publicized warfarin-interacting genes Cyp2c9 and Vkorc1 emerged from preliminary analyses. However, novel sex-specific effects were observed...

..Patient genotypes at two loci, CYP2C9 and VKORC1, will be utilized, as variants of these genes are closely associated with the reduced effectiveness of ..

..The Iong-term aim of this research is to determine the clinical consequences of genetic variability within the human CYP2C9 gene among subjects of diverse ethnic origins, and to understand molecular mechanisms that underlie genetically-..

..affecting the function of the serotonin transporter will predict responses to CU', whereas polymorphism of CYP2C 19 will be associated with the side effect profiles and pharmacokinetics of CIT...

..acid (11,12-EET), the putative endothelium derived hyperpolarizing factor (EDHF)is formed by the enzymes CYP2C9, CYP2C8, and converted to its corresponding dihydroxy metabolite (DHET) by soluble epoxide hydrolase (sEH)...

..The new computational methods will be applied to two CYP enzymes (CYP2C9, 3A4) important in drug metabolism...

..Part 1: A cocktail to include: caffeine (CYP1A2), flurbiprofen (CYP2C9), mephenytoin (CYP2C19), debrisoquine (CYP2D6), chlorzoxazone (CYP2E1) and dapsone (acetylation)...

..probes for enzymes that metabolize and transport most clinically used drugs: caffeine (CYP1A2), losartan (CYP2C9), dextromethorphan (CYP2D6?also probes for CYP3A4), buspirone (CYP3A4), and fexofenadine (P-gp), in addition to ..