Cytochrome P450 enzymes in drug metabolism: Regulation of gene expression, enzyme activities, and impact of genetic variation¶
Zanger, U. M., & Schwab, M. (2013). Cytochrome P450 enzymes in drug metabolism: Regulation of gene expression, enzyme activities, and impact of genetic variation: Regulation of gene expression, enzyme activities, and impact of genetic variation. Pharmacology & Therapeutics.
Cited by¶
3 citations across 3 artifacts.
Each citation links to the sentence it supports in the citing article.
Domain-specific¶
- Elimination Pathway
- The principal routes are hepatic metabolism — Phase I oxidative biotransformation primarily by cytochrome P450 enzymes (especially CYP3A4, CYP2D6, CYP2C9, and CYP2C19)
This sourceThe finding that about a dozen CYP450 enzymes of the CYP1, 2 and 3 families, including hepatic CYP3A4, CYP2C9, CYP2D6 and CYP2C19, carry most drug biotransformation.
Supported in partVerified against the publisher's abstract
“Of 57 putatively functional human CYPs only about a dozen enzymes, belonging to the CYP1, 2, and 3 families, are responsible for the biotransformation of most foreign substances including 70-80% of all drugs in clinical use.”
- The principal routes are hepatic metabolism — Phase I oxidative biotransformation primarily by cytochrome P450 enzymes (especially CYP3A4, CYP2D6, CYP2C9, and CYP2C19)
- Enzyme Inhibition
- Inhibitors of metabolic isoforms (azoles and macrolides on CYP3A4, SSRIs like fluoxetine and paroxetine on CYP2D6)
This sourceReview of cytochrome P450 enzymes in drug metabolism, naming CYP3A4 and CYP2D6 among the isoforms that metabolise most drugs in clinical use.
Supported in partVerified against the publisher's abstract
“The highest expressed forms in liver are CYPs 3A4, 2C9, 2C8, 2E1, and 1A2, while 2A6, 2D6, 2B6, 2C19 and 3A5 are less abundant”
- Inhibitors of metabolic isoforms (azoles and macrolides on CYP3A4, SSRIs like fluoxetine and paroxetine on CYP2D6)
- Metabolic Inactivation
- The process determines a drug's or toxin's half-life and therefore its dosing interval; it explains drug-drug interactions when two compounds compete for the same cytochrome isoform or when one induces or inhibits the enzyme system processing the other; and it accounts for individual variability in drug response arising from genetic polymorphisms in P450 genes (notably CYP2D6, CYP2C19, and CYP2C9; CYP3A4 polymorphisms are generally less predictive) that produce poor, intermediate, extensive, or ultrarapid metabolizer phenotypes
This sourceA review of how genetic polymorphisms in CYP2D6, CYP2C19, CYP2C9 and other P450s yield poor, intermediate, extensive and ultrarapid metabolizer phenotypes, with CYP3A4 variants noted as generally less predictive.
Supported in partVerified against the source
- The process determines a drug's or toxin's half-life and therefore its dosing interval; it explains drug-drug interactions when two compounds compete for the same cytochrome isoform or when one induces or inhibits the enzyme system processing the other; and it accounts for individual variability in drug response arising from genetic polymorphisms in P450 genes (notably CYP2D6, CYP2C19, and CYP2C9; CYP3A4 polymorphisms are generally less predictive) that produce poor, intermediate, extensive, or ultrarapid metabolizer phenotypes
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