User:MDElliottMD/Sandbox/CYP2C9: Difference between revisions
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MDElliottMD (talk | contribs) Expand CYP2C9 substrate section per Mark 2026-05-19 Option C decision: replace bullet list with 36-row sortable wikitable (substrate / therapeutic class / CYP2C9 contribution tier / clinical notes) covering anticoagulants, antiepileptics, NSAIDs, sulfonylureas, ARBs, statins, cannabinoids, antifungals, others. Add Comprehensive-tables pointer section naming Flockhart Indiana University table, FDA Drug Development table, PharmGKB (cited Whirl-Carrillo 2021 PMID 34216021). Add Zanger and Schwab... |
MDElliottMD (talk | contribs) Expand CYP2C9 substrate section per Mark 2026-05-19 Option C decision: replace bullet list with 36-row sortable wikitable (substrate / therapeutic class / CYP2C9 contribution tier / clinical notes) covering anticoagulants, antiepileptics, NSAIDs, sulfonylureas, ARBs, statins, cannabinoids, antifungals, others. Add Comprehensive-tables pointer section naming Flockhart Indiana University table, FDA Drug Development table, PharmGKB (cited Whirl-Carrillo 2021 PMID 34216021). Add Zanger and Schwab... |
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CYP2C9 catalyzes hydroxylation, epoxidation, and N- and O-dealkylation across a substrate spectrum that, while narrower than CYP3A4's, contains a striking concentration of medicines with narrow therapeutic windows and well-defined dose-response toxicities. The combination of warfarin and phenytoin alone, both of which are major CYP2C9 substrates with narrow therapeutic windows, accounts for a substantial share of the inpatient pharmacogenomic-testing case that has been built around this enzyme over the last two decades.<ref name="zanger2013">Zanger UM, Schwab M. Cytochrome P450 enzymes in drug metabolism: regulation of gene expression, enzyme activities, and impact of genetic variation. ''Pharmacology and Therapeutics''. 2013 Apr;138(1):103-141. PMID: 23333322.</ref> | CYP2C9 catalyzes hydroxylation, epoxidation, and N- and O-dealkylation across a substrate spectrum that, while narrower than CYP3A4's, contains a striking concentration of medicines with narrow therapeutic windows and well-defined dose-response toxicities. The combination of warfarin and phenytoin alone, both of which are major CYP2C9 substrates with narrow therapeutic windows, accounts for a substantial share of the inpatient pharmacogenomic-testing case that has been built around this enzyme over the last two decades.<ref name="zanger2013">Zanger UM, Schwab M. Cytochrome P450 enzymes in drug metabolism: regulation of gene expression, enzyme activities, and impact of genetic variation. ''Pharmacology and Therapeutics''. 2013 Apr;138(1):103-141. PMID: 23333322.</ref> | ||
The table below collects the clinically important CYP2C9 substrates by therapeutic class, with each entry tagged by the contribution CYP2C9 makes to overall clearance: '''major''' (CYP2C9 is the predominant route; genotype-modulated and inhibitor-modulated interactions are clinically expected), '''moderate''' (CYP2C9 contributes meaningfully but other routes carry comparable load), and '''minor''' (CYP2C9 contributes but other pathways dominate). The list is curated for clinical relevance and is not exhaustive; see [[#Comprehensive substrate and interaction tables|Comprehensive substrate and interaction tables]] below for the authoritative maintained resources. | The table below collects the clinically important CYP2C9 substrates by therapeutic class, with each entry tagged by the contribution CYP2C9 makes to overall clearance: '''major''' (CYP2C9 is the predominant route; genotype-modulated and inhibitor-modulated interactions are clinically expected), '''moderate''' (CYP2C9 contributes meaningfully but other routes carry comparable load), and '''minor''' (CYP2C9 contributes but other pathways dominate). The list is curated for clinical relevance and is not exhaustive; see [[#Comprehensive substrate and interaction tables|Comprehensive substrate and interaction tables]] below for the authoritative maintained resources. ''Click '''Expand''' at right to view the table.'' | ||
{| class="wikitable sortable" | {| class="wikitable sortable mw-collapsible mw-collapsed" | ||
|+ CYP2C9 substrate table (click to expand) | |||
! Substrate !! Therapeutic class !! CYP2C9 contribution !! Clinical notes | ! Substrate !! Therapeutic class !! CYP2C9 contribution !! Clinical notes | ||
|- | |- | ||