What is CYP2C9 genotype?
CYP2C9 Genotyping Of special interest are those drugs with narrow therapeutic index, such as warfarin (Coumadin®), tolbutamide, and phenytoin (Dilantin®), where impairment in CYP2C9 metabolic activity might cause difficulties in dose adjustment as well as toxicity. VKORC1 is the site of action of warfarin.
What is the important of CYP2C9 gene?
The CYP2C9 enzyme also plays a major role in breaking down the drug warfarin, which thins the blood and prevents blood clots from forming. This enzyme also assists in metabolizing other drugs such as ibuprofen, which reduces inflammation.
What is the role of cytochrome P450 in drug metabolism?
Cytochrome P450 enzymes are essential for the metabolism of many medications. Cytochrome P450 enzymes can be inhibited or induced by drugs, resulting in clinically significant drug-drug interactions that can cause unanticipated adverse reactions or therapeutic failures.
What is the chromosomal location of the CYP2C9 gene?
The enzyme is involved in metabolism, by oxidation, of both xenobiotics, including drugs, and endogenous compounds, including fatty acids. In humans, the protein is encoded by the CYP2C9 gene….
| CYP2C9 | ||
|---|---|---|
| Location (UCSC) | Chr 10: 94.94 – 94.99 Mb | Chr 19: 39.06 – 39.09 Mb |
| PubMed search | ||
| Wikidata | ||
| View/Edit Human View/Edit Mouse |
What are CYP2C9 inhibitors?
CYP2C9 is inhibited by amiodarone, fluconazole, and sulphaphenazole among other drugs [9]. Dangerous drug- drug interaction can arise when an inhibitor such as one of these is added to a therapeutic regime that includes drugs with a low therapeutic index, such as S-warfarin, tolbutamine, and phenytoin [40-42].
Which drugs are metabolised by CYP2C9?
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. CYP2C9 activity in vivo is inducible by rifampicin.
Is CYP2C9 polymorphic?
CYP2C9 is highly polymorphic, with a total of 61 alleles reported, all of which have either reduced or no enzymatic activity. A patient’s phenotype is calculated based on the genotype of the CYP2C9 allele, its heterozygosity or homozygosity (also referred to as diplotype).
Is warfarin a CYP inhibitor?
Furthermore, warfarin alcohols are known to competitively inhibit CYP2C9 yet are not metabolized (15). Hydroxywarfarins may similarly retain affinity for the CYP2C9 active site. Hydroxywarfarin plasma levels will also play an important role in driving these inhibitory interactions.
Cytochrome P450: genotype to phenotype The cytochromes P450 comprise a family of enzymes that are responsible for around three-quarters of all drug metabolism reactions that occur in human populations. Many isoforms of cytochrome P450 exist but most reactions are undertaken by CYP2C9, CYP2C19, CYP2D6 and CYP3A4.
Who are the authors of cytochrome P450 2c9-cyp2c9?
Cytochrome P450 2C9-CYP2C9 Derek Van Booven,aSharon Marsh,bHoward McLeod,cMichelle Whirl Carrillo,dKatrin Sangkuhl,dTeri E. Klein,dand Russ B. Altmand,e Derek Van Booven
What is the Order of the CYP2C9 genes?
The cluster comprises four genes arranged in the order CYP2C8-CYP2C9-CYP2C19-CYP2C18[1]. Several studies identified a single nucleotide polymorphism (SNP) linkage between the CYP2C8and CYP2C9genes [2-4].
What kind of enzyme is CYP2C9 in warfarin?
CYP2C9 is the enzyme responsible for the metabolism of the S-isomer of warfarin that is principally responsible for the anticoagulant effect of the drug. The crystal structure of human CYP2C9 was described by Williams et al.