Cytochrome P-450: Difference between revisions
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===CYP2C19=== | ===CYP2C19=== | ||
''CYP2C19'' is an [[isoenzyme]] of cytochrome P-450.<ref>{{OMIM|124020}}</ref> 2-6% of anglos and 15-25% of asians are poor metabolizers of drugs that use the CYP2C19 [[isoenzyme]].<ref name="pmid11710893">{{cite journal |author=Phillips KA, Veenstra DL, Oren E, Lee JK, Sadee W |title=Potential role of pharmacogenomics in reducing adverse drug reactions: a systematic review |journal=JAMA |volume=286 |issue=18 |pages=2270–9 |year=2001 |month=November |pmid=11710893 |doi= |url=http://jama.ama-assn.org/cgi/pmidlookup?view=long&pmid=11710893 |issn=}}</ref><ref name="pmid12571261">{{cite journal |author=Weinshilboum R |title=Inheritance and drug response |journal=N. Engl. J. Med. |volume=348 |issue=6 |pages=529–37 |year=2003 |month=February |pmid=12571261 |doi=10.1056/NEJMra020021 |url=http://content.nejm.org/cgi/pmidlookup?view=short&pmid=12571261&promo=ONFLNS19 |issn=}}</ref> More recently, a study suggests that 30% of patients may have a reduced-function allele.<ref name="pmid19106084">{{cite journal |author=Mega JL, Close SL, Wiviott SD, ''et al'' |title=Cytochrome P-450 Polymorphisms and Response to Clopidogrel |journal=N. Engl. J. Med. |volume= |issue= |pages= |year=2008 |month=December |pmid=19106084 |doi=10.1056/NEJMoa0809171 |url=http://content.nejm.org/cgi/pmidlookup?view=short&pmid=19106084&promo=ONFLNS19 |issn=}}</ref> | ''CYP2C19'' is an [[isoenzyme]] of cytochrome P-450.<ref>{{OMIM|124020}}</ref> 2-6% of anglos and 15-25% of asians are poor metabolizers of drugs that use the CYP2C19 [[isoenzyme]].<ref name="pmid11710893">{{cite journal |author=Phillips KA, Veenstra DL, Oren E, Lee JK, Sadee W |title=Potential role of pharmacogenomics in reducing adverse drug reactions: a systematic review |journal=JAMA |volume=286 |issue=18 |pages=2270–9 |year=2001 |month=November |pmid=11710893 |doi= |url=http://jama.ama-assn.org/cgi/pmidlookup?view=long&pmid=11710893 |issn=}}</ref><ref name="pmid12571261">{{cite journal |author=Weinshilboum R |title=Inheritance and drug response |journal=N. Engl. J. Med. |volume=348 |issue=6 |pages=529–37 |year=2003 |month=February |pmid=12571261 |doi=10.1056/NEJMra020021 |url=http://content.nejm.org/cgi/pmidlookup?view=short&pmid=12571261&promo=ONFLNS19 |issn=}}</ref> More recently, a study suggests that 30% of patients may have a reduced-function allele.<ref name="pmid19106084">{{cite journal |author=Mega JL, Close SL, Wiviott SD, ''et al'' |title=Cytochrome P-450 Polymorphisms and Response to Clopidogrel |journal=N. Engl. J. Med. |volume= |issue= |pages= |year=2008 |month=December |pmid=19106084 |doi=10.1056/NEJMoa0809171 |url=http://content.nejm.org/cgi/pmidlookup?view=short&pmid=19106084&promo=ONFLNS19 |issn=}}</ref> | ||
CYP2C19 polymorphism affects response to [[clopidogrel]]. CYP2C19 loss-of-function alleles are associated with more cardiovascular events.<ref name="pmid19106083">{{cite journal |author=Simon T, Verstuyft C, Mary-Krause M, ''et al.'' |title=Genetic determinants of response to clopidogrel and cardiovascular events |journal=N. Engl. J. Med. |volume=360 |issue=4 |pages=363–75 |year=2009 |month=January |pmid=19106083 |doi=10.1056/NEJMoa0808227 |url=http://content.nejm.org/cgi/pmidlookup?view=short&pmid=19106083&promo=ONFLNS19 |issn=}}</ref> Concomitant [[proton pump inhibitor]]s, which are also metabolized by CYP2C19, may<ref name="pmid19258584">{{cite journal |author=Ho PM, Maddox TM, Wang L, ''et al.'' |title=Risk of adverse outcomes associated with concomitant use of clopidogrel and proton pump inhibitors following acute coronary syndrome |journal=JAMA |volume=301 |issue=9 |pages=937–44 |year=2009 |month=March |pmid=19258584 |doi=10.1001/jama.2009.261 |url=http://jama.ama-assn.org/cgi/pmidlookup?view=long&pmid=19258584 |issn=}}</ref> (especially inhibitors other than [[pantoprazole]]<ref name="pmid19176635">Juurlink DN, Gomes T, Ko DT, Szmitko PE, Austin PC, Tu JV, Henry DA, Kopp A, Mamdani MM. A population-based study of the drug interaction between proton pump inhibitors and clopidogrel. CMAJ. 2009 Mar 31;180(7):713-8. Epub 2009 Jan 28. PMID 19176635</ref>) or may not<ref name="pmid19106083">{{cite journal |author=Simon T, Verstuyft C, Mary-Krause M, ''et al.'' |title=Genetic determinants of response to clopidogrel and cardiovascular events |journal=N. Engl. J. Med. |volume=360 |issue=4 |pages=363–75 |year=2009 |month=January |pmid=19106083 |doi=10.1056/NEJMoa0808227 |url=http://content.nejm.org/cgi/pmidlookup?view=short&pmid=19106083&promo=ONFLNS19 |issn=}}</ref> increase adverse cardiac events. | CYP2C19 polymorphism affects response to [[clopidogrel]]. CYP2C19 loss-of-function alleles are associated with more cardiovascular events.<ref name="pmid19106083">{{cite journal |author=Simon T, Verstuyft C, Mary-Krause M, ''et al.'' |title=Genetic determinants of response to clopidogrel and cardiovascular events |journal=N. Engl. J. Med. |volume=360 |issue=4 |pages=363–75 |year=2009 |month=January |pmid=19106083 |doi=10.1056/NEJMoa0808227 |url=http://content.nejm.org/cgi/pmidlookup?view=short&pmid=19106083&promo=ONFLNS19 |issn=}}</ref> Concomitant [[proton pump inhibitor]]s, which are also metabolized by CYP2C19, may<ref name="pmid19258584">{{cite journal |author=Ho PM, Maddox TM, Wang L, ''et al.'' |title=Risk of adverse outcomes associated with concomitant use of clopidogrel and proton pump inhibitors following acute coronary syndrome |journal=JAMA |volume=301 |issue=9 |pages=937–44 |year=2009 |month=March |pmid=19258584 |doi=10.1001/jama.2009.261 |url=http://jama.ama-assn.org/cgi/pmidlookup?view=long&pmid=19258584 |issn=}}</ref> (especially inhibitors other than [[pantoprazole]]<ref name="pmid19176635">Juurlink DN, Gomes T, Ko DT, Szmitko PE, Austin PC, Tu JV, Henry DA, Kopp A, Mamdani MM. A population-based study of the drug interaction between proton pump inhibitors and clopidogrel. CMAJ. 2009 Mar 31;180(7):713-8. Epub 2009 Jan 28. PMID 19176635</ref>) or may not<ref name="pmid19106083">{{cite journal |author=Simon T, Verstuyft C, Mary-Krause M, ''et al.'' |title=Genetic determinants of response to clopidogrel and cardiovascular events |journal=N. Engl. J. Med. |volume=360 |issue=4 |pages=363–75 |year=2009 |month=January |pmid=19106083 |doi=10.1056/NEJMoa0808227 |url=http://content.nejm.org/cgi/pmidlookup?view=short&pmid=19106083&promo=ONFLNS19 |issn=}}</ref> increase adverse cardiac events. | ||
Revision as of 21:04, 9 October 2009
CYP2C19
CYP2C19 is an isoenzyme of cytochrome P-450.[1] 2-6% of anglos and 15-25% of asians are poor metabolizers of drugs that use the CYP2C19 isoenzyme.[2][3] More recently, a study suggests that 30% of patients may have a reduced-function allele.[4]
CYP2C19 polymorphism affects response to clopidogrel. CYP2C19 loss-of-function alleles are associated with more cardiovascular events.[5] Concomitant proton pump inhibitors, which are also metabolized by CYP2C19, may[6] (especially inhibitors other than pantoprazole[7]) or may not[5] increase adverse cardiac events.
- ↑ Online Mendelian Inheritance in Man, OMIM®. Johns Hopkins University, Baltimore, MD. MIM Number: 124020. World Wide Web URL: http://omim.org/.
- ↑ Phillips KA, Veenstra DL, Oren E, Lee JK, Sadee W (November 2001). "Potential role of pharmacogenomics in reducing adverse drug reactions: a systematic review". JAMA 286 (18): 2270–9. PMID 11710893. [e]
- ↑ Weinshilboum R (February 2003). "Inheritance and drug response". N. Engl. J. Med. 348 (6): 529–37. DOI:10.1056/NEJMra020021. PMID 12571261. Research Blogging.
- ↑ Mega JL, Close SL, Wiviott SD, et al (December 2008). "Cytochrome P-450 Polymorphisms and Response to Clopidogrel". N. Engl. J. Med.. DOI:10.1056/NEJMoa0809171. PMID 19106084. Research Blogging.
- ↑ 5.0 5.1 Simon T, Verstuyft C, Mary-Krause M, et al. (January 2009). "Genetic determinants of response to clopidogrel and cardiovascular events". N. Engl. J. Med. 360 (4): 363–75. DOI:10.1056/NEJMoa0808227. PMID 19106083. Research Blogging.
- ↑ Ho PM, Maddox TM, Wang L, et al. (March 2009). "Risk of adverse outcomes associated with concomitant use of clopidogrel and proton pump inhibitors following acute coronary syndrome". JAMA 301 (9): 937–44. DOI:10.1001/jama.2009.261. PMID 19258584. Research Blogging.
- ↑ Juurlink DN, Gomes T, Ko DT, Szmitko PE, Austin PC, Tu JV, Henry DA, Kopp A, Mamdani MM. A population-based study of the drug interaction between proton pump inhibitors and clopidogrel. CMAJ. 2009 Mar 31;180(7):713-8. Epub 2009 Jan 28. PMID 19176635