Enzyme:CYP3A4: Difference between revisions
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MDElliottMD (talk | contribs) Consolidate enzyme entity page to canonical Pharmacopedia: sandbox location per Mark 2026-05-19. Full retrofitted version: history-first spine, collapsible-sortable substrate table, comprehensive-tables pointer, all PMIDs NCBI-eutils-verified, zero em-dashes. For CYP2D6/CYP3A4/CYP2C19 this replaces the earlier pre-retrofit draft with the full version; for the other 8 enzymes this is the first save at the canonical location. Resolves a cross-session sandbox-location duplication: the User:MDEll... |
MDElliottMD (talk | contribs) Revise CYP3A4 Phenotype categories section per parser-claude 2026-05-20: the earlier text flatly stated CYP3A4 has no metabolizer-phenotype classification. That is true for CPIC but not for DPWG, which tiers CYP3A4 into PM/IM/NM on the CYP3A4*22 allele. New text states the CPIC/DPWG disagreement, links the three Phenotype:CYP3A4 pages, and keeps the point that environmental induction/inhibition dominate CYP3A4 variability. Cites DPWG guideline PharmGKB PA166265421. See-also gains the three ph... |
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== Phenotype categories == | == Phenotype categories == | ||
CYP3A4 phenotyping is a more contested matter than the phenotyping of [[Enzyme:CYP2D6|CYP2D6]] or the CYP2C enzymes, and the two major pharmacogenomics consortia do not agree on it. The Clinical Pharmacogenetics Implementation Consortium (CPIC) does not assign CYP3A4 a metabolizer-phenotype classification; in CPIC's framing the population variability in CYP3A4 activity, though wide (roughly 10- to 30-fold between individuals), is dominated by environmental and physiological factors rather than by frankly inactivating star-allele genetics. The Dutch Pharmacogenetics Working Group (DPWG) takes the other position and does define a CYP3A4 phenotype, built around the decreased-function ''CYP3A4\*22'' allele: a poor metabolizer carries two ''\*22'' alleles, an intermediate metabolizer one, and a normal metabolizer none. The DPWG framework underlies that group's guidance on, for example, quetiapine dosing.<ref name="dpwg-cyp3a4">Dutch Pharmacogenetics Working Group (DPWG). Gene-drug interaction guideline for CYP3A4 (PharmGKB guideline annotation PA166265421). Royal Dutch Pharmacists Association (KNMP). Available via https://www.pharmgkb.org/.</ref> The wiki indexes the DPWG phenotype categories at [[Phenotype:CYP3A4 poor metabolizer]], [[Phenotype:CYP3A4 intermediate metabolizer]], and [[Phenotype:CYP3A4 normal metabolizer]]. Even under the DPWG framework, the CYP3A4 phenotype is a less settled construct than the CYP2D6 or CYP2C19 phenotypes, and environmental induction and inhibition remain the dominant sources of CYP3A4 variability whatever a patient's ''\*22'' genotype. | |||
== Major variants == | == Major variants == | ||
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* [[Enzyme:CYP3A5]], the related isoform with the more clinically actionable polymorphism | * [[Enzyme:CYP3A5]], the related isoform with the more clinically actionable polymorphism | ||
* [[Enzyme:CYP2D6]], [[Enzyme:CYP2C19]], [[Enzyme:CYP2C9]], [[Enzyme:CYP1A2]], [[Enzyme:CYP2B6]] | * [[Enzyme:CYP2D6]], [[Enzyme:CYP2C19]], [[Enzyme:CYP2C9]], [[Enzyme:CYP1A2]], [[Enzyme:CYP2B6]] | ||
* [[Phenotype:CYP3A4 poor metabolizer]], [[Phenotype:CYP3A4 intermediate metabolizer]], [[Phenotype:CYP3A4 normal metabolizer]] (the DPWG CYP3A4 metabolizer phenotypes) | |||
* [[Tacrolimus]], [[Simvastatin]], [[Midazolam]], [[Cyclosporine]] (canonical CYP3A4 substrate examples) | * [[Tacrolimus]], [[Simvastatin]], [[Midazolam]], [[Cyclosporine]] (canonical CYP3A4 substrate examples) | ||
* [[Rifampin]], [[Clarithromycin]], grapefruit juice (canonical inducer and inhibitor examples) | * [[Rifampin]], [[Clarithromycin]], grapefruit juice (canonical inducer and inhibitor examples) | ||