CYP2C19
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Cytochrome P450 2C19 (abbreviated CYP2C19) is an enzyme. This protein, a member of the cytochrome P450 mixed-function oxidase system, is involved in the metabolism of xenobiotics, including many proton pump inhibitors and antiepileptics. In humans, the CYP2C19 protein is encoded by the CYP2C19 gene.[1][2] CYP2C19 is a liver enzyme that acts on 10-15% of drugs in current clinical use,[3] including the antiplatelet clopidogrel (Plavix), drugs that treat pain associated with ulcers, such as omeprazole, antiseizure drugs such as mephenytoin, the antimalarial proguanil, and the anxiolytic diazepam.[4]
CYP2C19 has been annotated as (R)-limonene 6-monooxygenase and (S)-limonene 6-monooxygenase in UniProt.
Contents
Function
The gene encodes a member of the cytochrome P450 superfamily of enzymes. These proteins are monooxygenases that catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids. This protein localizes to the endoplasmic reticulum and is known to metabolize many drugs. Polymorphism within this gene is associated with variable ability to metabolize mephenytoin, known as the poor metabolizer and extensive metabolizer phenotypes. The gene is located within a cluster of cytochrome P450 genes on chromosome no.10 arm q24.[5]
Genetic polymorphism and pharmacogenomics
Genetic polymorphism (mainly CYP2C19*2, CYP2C19*3 and CYP2C19*17) exists for CYP2C19 expression, with approximately 3–5% of Caucasian and 15–20% of Asian populations being poor metabolizers with no CYP2C19 function.[6][7] This may reduce the efficacy of clopidogrel (Plavix). In patients with an abnormal CYP2C19 variant certain benzodiazepines should be avoided, such as diazepam (Valium), lorazepam (Ativan), oxazepam (Serax), and temazepam (Restoril).[8] On the basis of their ability to metabolize (S)-mephenytoin or other CYP2C19 substrates, individuals can be classified as extensive metabolizers (EM) or poor metabolizers (PM).[7] Eight variant alleles (CYP2C19*2 to CYP2C19*8) that predict PMs have been identified.[7]
Ligands
The following is a table of selected substrates, inducers and inhibitors of CYP2C19. Where classes of agents are listed, there may be exceptions within the class.
Inhibitors of CYP2C19 can be classified by their potency, such as:
- Strong being one that causes at least a 5-fold increase in the plasma AUC values, or more than 80% decrease in clearance.[9]
- Moderate being one that causes at least a 2-fold increase in the plasma AUC values, or 50-80% decrease in clearance.[9]
- Weak being one that causes at least a 1.25-fold but less than 2-fold increase in the plasma AUC values, or 20-50% decrease in clearance.[9]
Substrates | Inhibitors | Inducers |
---|---|---|
|
Strong:
Weak:
|
|
See also
References
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External links
Further reading
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- ↑ 7.0 7.1 7.2 Desta, Z., et al. (2002). Clinical significance of the cytochrome P450 2C19 genetic polymorphism. Clin Pharmacokinet 41(12) 913-58. PMID 12222994
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- ↑ 9.00 9.01 9.02 9.03 9.04 9.05 9.06 9.07 9.08 9.09 9.10 9.11 9.12 9.13 9.14 9.15 9.16 9.17 9.18 9.19 9.20 9.21 9.22 9.23 9.24 9.25 9.26 9.27 9.28 9.29 9.30 9.31 9.32 9.33 9.34 9.35 9.36 9.37 9.38 9.39 9.40 9.41 9.42 9.43 Lua error in package.lua at line 80: module 'strict' not found. Retrieved on July 2011
- ↑ 10.00 10.01 10.02 10.03 10.04 10.05 10.06 10.07 10.08 10.09 10.10 10.11 10.12 10.13 10.14 10.15 10.16 10.17 10.18 10.19 FASS (drug formulary): Swedish environmental classification of pharmaceuticals Facts for prescribers (Fakta för förskrivare). Retrieved July 2011
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- ↑ Clin Pharmacol Ther. 2003 Mar;73(3):264-71. Isozyme-specific induction of low-dose aspirin on cytochrome P450 in healthy subjects. Chen XP1, Tan ZR, Huang SL, Huang Z, Ou-Yang DS, Zhou HH.