Drug Metabolism Disorders (CYP450 Pharmacogenomics)
Prevalence: 7-10% of Caucasians are CYP2D6 poor metabolizers; 2-5% are CYP2C19 poor metabolizers
Genetic variation in cytochrome P450 enzymes (CYP2D6, CYP2C19, CYP2C9) creates a spectrum from ultra-rapid to poor metabolizers. This affects ~25% of all prescribed medications and is the foundation of clinical pharmacogenomics.
Peptide Therapeutics
Peptide drugs that bypass CYP450 metabolism entirely offer consistent efficacy regardless of metabolizer status. Peptides are typically degraded by proteases rather than CYP enzymes, making them inherently pharmacogenomics-resistant.
Current Treatments
Genotype-guided drug selection and dosing per CPIC guidelines. Alternative drugs chosen based on metabolizer status.
Key Genetic Variants
CYP2D6 — CYP2D6*4 (splicing defect)
CYP2C19 — CYP2C19*2 (splicing defect)
CYP2C19 — CYP2C19*17 (-806C>T)
CYP2C9 — CYP2C9*2 (Arg144Cys)
CYP2C9 — CYP2C9*3 (Ile359Leu)
Associated Genes
Phase I drug metabolism enzyme responsible for ~25% of clinical drugs. Highly polymorphic with >100 known alleles ranging from gene deletion to ultra-rapid multiplication.
CYP2C19Cytochrome P450 2C19Metabolizes proton pump inhibitors, clopidogrel, certain antidepressants, and antifungals. Pharmacogenomic testing is recommended before clopidogrel therapy by CPIC guidelines.
CYP2C9Cytochrome P450 2C9Metabolizes ~15% of clinical drugs including warfarin (S-enantiomer), NSAIDs, sulfonylureas, and losartan. CYP2C9 genotype is part of FDA warfarin dosing guidelines.
Explore peptide candidates for Drug Metabolism Disorders (CYP450 Pharmacogenomics)
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