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Cytochrome P450, family 2, subfamily C, polypeptide 8

CYP2C8
This gene encodes a member of the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are monooxygenases which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids. This protein localizes to the endoplasmic reticulum and its expression is induced by phenobarbital. The enzyme is known to metabolize many xenobiotics, including the anticonvulsive drug mephenytoin, benzo(a)pyrene, 7-ethyoxycoumarin, and the anti-cancer drug taxol. This gene is located within a cluster of cytochrome P450 genes on chromosome 10q24. Several transcript variants encoding a few different isoforms have been found for this gene. [provided by RefSeq, Nov 2010] (from NCBI)
Top mentioned proteins: CYP3A4, CYP2C9, Cyp, CYP2C19, CYP1A1
Papers on CYP2C8
Testing of candidate single nucleotide variants associated with paclitaxel neuropathy in the trial NCCTG N08C1 (Alliance).
New
Beutler et al., Rochester, United States. In Cancer Med, Feb 2016
None of the other results supported the previously reported associations, including some SNVs displaying an opposite direction of effect from previous reports, including rs1058930 in CYP2C8, rs17222723 and rs8187710 in ABCC2, rs10771973 in FGD4, rs16916932 in CACNB2 and rs16948748 in PITPNA.
Role of Cytochrome P450 2C8 in Drug Metabolism and Interactions.
Review
New
Impact
Neuvonen et al., Helsinki, Finland. In Pharmacol Rev, Jan 2016
CYP2C8 is highly expressed in human liver and is known to metabolize more than 100 drugs.
In vitro evaluation of hepatotoxic drugs in human hepatocytes from multiple donors: Identification of P450 activity as a potential risk factor for drug-induced liver injuries.
New
Li et al., Columbia, United States. In Chem Biol Interact, Jan 2016
Human hepatocytes from 19 donors were evaluated for the activities of 8 major P450 isoforms: CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1 and CYP3A4.
Contribution of major metabolites towards complex drug-drug interactions of deleobuvir: in vitro predictions and in vivo outcomes.
New
Tweedie et al., Ottawa, Canada. In Drug Metab Dispos, Jan 2016
Of note was more potent CYP2C8 inactivation by deleobuvir-AG than deleobuvir and CYP450 induction by CD 6168 but not by deleobuvir.
Genetic polymorphisms and paclitaxel- or docetaxel-induced toxicities: A systematic review.
Review
New
Boven et al., Amsterdam, Netherlands. In Cancer Treat Rev, Dec 2015
Inconclusive data for risk of toxicity as well as for effects on drug exposure were reported on variants in ABCB1, CYP3A4, CYP3A5 and, for paclitaxel, CYP2C8.
Effect of penicillin-based antibiotics, amoxicillin, ampicillin, and piperacillin, on drug-metabolizing activities of human hepatic cytochromes P450.
New
Imagawa et al., In J Toxicol Sci, Dec 2015
However, amoxicillin and piperacillin inhibited CYP2C8-mediated aminopyrine N-demethylation at 50% inhibitory concentration of 0.83 and 1.14 mM, respectively.
Ferrous and ferric state of cytochromes P450 in intact Escherichia coli cells: a possible role of cytochrome P450-flavodoxin interactions.
New
Martinek et al., Praha, Czech Republic. In Neuro Endocrinol Lett, Nov 2015
CONCLUSION: Depending on the resting state, the CYPs heterologously expressed in E. coli could be divided into two groups; CYP2C8, 2C9, 3A4 are in E. coli present mainly in the oxidized form; while CYP1A1, 1A2, 2A6, 2A13, 2B6, 2D6 are found predominantly in the reduced form.
Sirolimus and everolimus in kidney transplantation.
Review
New
de Fijter et al., Leiden, Netherlands. In Drug Discov Today, Oct 2015
They are metabolized by cytochrome (CYP)-3A4/5 and CYP2C8 enzymes and are substrates for P-glycoprotein (P-gp).
Pharmacogenomics of glinides.
Review
Jia et al., Shanghai, China. In Pharmacogenomics, 2015
Polymorphisms of genes involved in drug metabolism, such as CYP2C9, CYP2C8 and SLCO1B1, may influence the efficacy of glinides and the incidence of adverse effects.
Effect of an ethanol extract of Descurainia sophia seeds on Phase I and II drug metabolizing enzymes and P-glycoprotein activity in vitro.
Kim et al., Taejŏn, South Korea. In Bmc Complement Altern Med, 2014
Other Phase I (CYP2C8, CYP2D6, and CYP3A4) and Phase II (UGT1A1 and UGT2B7) enzymes as well as P-gp were weakly or negligibly affected by EEDS with concentrations up to 500 μg/mL.
Pharmacokinetic drug interactions with clopidogrel: updated review and risk management in combination therapy.
Review
Zhou et al., Hangzhou, China. In Ther Clin Risk Manag, 2014
The mechanism of the DDIs with clopidogrel involves modulating CYP enzymes (eg, CYP2B6, CYP2C8, CYP2C19, and CYP3A4), paraoxonase-1, hepatic carboxylesterase 1, P-glycoprotein, and organic anion transporter family member 1B1.
The effects of febuxostat on the pharmacokinetic parameters of rosiglitazone, a CYP2C8 substrate.
GeneRIF
McLean et al., Deerfield, United States. In Br J Clin Pharmacol, 2012
Co-administration of febuxostat had no effect on rosiglitazone or N-desmethylrosiglitazone pharmacokinetics, suggesting that febuxostat can be given safely with drugs metabolized through CYP2C8.
Genetic polymorphisms of CYP2C8 in the Czech Republic.
GeneRIF
Slanar et al., Praha, Czech Republic. In Genet Test Mol Biomarkers, 2012
Allele frequencies of functionally important CYP2C8 variants in the Czech population are similar to that of other Caucasian populations.
CYP2C8*3 predicts benefit/risk profile in breast cancer patients receiving neoadjuvant paclitaxel.
GeneRIF
Dees et al., Chapel Hill, United States. In Breast Cancer Res Treat, 2012
CYP2C8 rs11572080, 416G-A and rs10509681, 1196A-G carriers are more likely to achieve complete clinical response to neoadjuvant paclitaxel in the treatment of breast cancer.
An unusual metabolic pathway of sipoglitazar, a novel antidiabetic agent: cytochrome P450-catalyzed oxidation of sipoglitazar acyl glucuronide.
GeneRIF
Asahi et al., Fujisawa, Japan. In Drug Metab Dispos, 2012
Data suggest that sipoglitazar is metabolized first by UGT to form an unstable acyl glucuronide, and this acyl glucuronide is then deethylated by CYP2C8.
Using genome-wide association studies to identify genes important in serious adverse drug reactions.
Review
Impact
Daly, Newcastle upon Tyne, United Kingdom. In Annu Rev Pharmacol Toxicol, 2011
Genome-wide studies have not yet found clear associations for drug-induced cardiotoxicity, but for bisphosphonate-induced necrosis of the jaw, polymorphisms in the cytochrome P450 CYP2C8 may predict susceptibility.
Endogenous epoxygenases are modulators of monocyte/macrophage activity.
GeneRIF
Bishop-Bailey et al., London, United Kingdom. In Plos One, 2010
monocytes and macrophages express the epoxygenases CYP2J2 and CYP2C8
Association of cytochrome P450 2C19 genotype with the antiplatelet effect and clinical efficacy of clopidogrel therapy.
Impact
Gurbel et al., Baltimore, United States. In Jama, 2009
Thirteen single-nucleotide polymorphisms on chromosome 10q24 within the CYP2C18-CYP2C19-CYP2C9-CYP2C8 cluster were associated with diminished clopidogrel response, with a high degree of statistical significance (P = 1.5 x 10(-13) for rs12777823, additive model).
Japanese-US common-arm analysis of paclitaxel plus carboplatin in advanced non-small-cell lung cancer: a model for assessing population-related pharmacogenomics.
Impact
Mack et al., Sacramento, United States. In J Clin Oncol, 2009
Genotypic variants of CYP3A4, CYP3A5, CYP2C8, NR1I2-206, ABCB1, ERCC1, and ERCC2 were analyzed by pyrosequencing or by PCR restriction fragment length polymorphism.
Pharmacogenetic assessment of toxicity and outcome after platinum plus taxane chemotherapy in ovarian cancer: the Scottish Randomised Trial in Ovarian Cancer.
Impact
Brown et al., Saint Louis, United States. In J Clin Oncol, 2007
PATIENTS AND METHODS: We assessed 27 selected polymorphisms based on previously described associations or putative functional effects in 16 key genes from pathways that may influence cellular sensitivity to taxanes (ABCB1, ABCC1, ABCC2, ABCG2, CDKN1A, CYP1B1, CYP2C8, CYP3A4, CYP3A5, MAPT, and TP53) and platinum (ABCC2, ABCG2, ERCC1, ERCC2, GSTP1, MPO, and XRCC1) using polymerase chain reaction and Pyrosequencing in 914 ovarian cancer patients from the Scottish Randomised Trial in Ovarian Cancer phase III trial who were treated at presentation with carboplatin and taxane regimens after cytoreductive surgery.
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