liminfoCYP450 Reference
Free reference guide: CYP450 Reference
About CYP450 Reference
The CYP450 Reference is a comprehensive, searchable guide to cytochrome P450 drug metabolism enzymes, covering major isoforms including CYP3A4 (responsible for ~50% of drug metabolism), CYP2D6 (~25%), CYP2C19, CYP2C9, CYP1A2, and CYP2B6 with their substrates, inhibitors, and inducers.
This reference includes pharmacogenomics data such as CYP2D6 metabolizer phenotypes (UM/EM/IM/PM), CPIC clinical guidelines for genotype-guided dosing, VKORC1 warfarin dosing, HLA drug hypersensitivity associations, and FDA pharmacogenomic biomarker labeling requirements.
Designed for pharmacists, physicians, clinical pharmacologists, and pharmacy students, this tool provides instant access to drug-enzyme relationships, interaction severity classifications, Phase I/Phase II metabolism pathways, and transporter information (P-gp, OATP) essential for safe prescribing.
Key Features
- Complete CYP3A4, CYP2D6, CYP2C19, CYP2C9, and CYP1A2 substrate, inhibitor, and inducer lists
- CYP2D6 metabolizer phenotype classification (Ultra-rapid, Normal, Intermediate, Poor) with clinical implications
- CPIC pharmacogenomics guidelines for Clopidogrel, Warfarin, Codeine, Tamoxifen, and thiopurines
- FDA inhibitor/inducer strength classification with AUC fold-change criteria (strong, moderate, weak)
- Drug transporter reference including P-glycoprotein (MDR1) and OATP1B1/SLCO1B1 interactions
- Phase II metabolism enzymes: UGT1A1 (Irinotecan), TPMT/NUDT15 (Azathioprine), DPYD (5-FU), NAT2
- HLA drug hypersensitivity associations: HLA-B*57:01 (Abacavir), HLA-B*15:02 (Carbamazepine), HLA-B*58:01 (Allopurinol)
- Real-world clinical case examples of CYP3A4 interactions including Simvastatin-Clarithromycin rhabdomyolysis
Frequently Asked Questions
Why is CYP3A4 the most important drug-metabolizing enzyme?
CYP3A4 metabolizes approximately 50% of all clinically used drugs, including statins (Simvastatin, Atorvastatin), immunosuppressants (Cyclosporine, Tacrolimus), benzodiazepines (Midazolam), calcium channel blockers (Felodipine), macrolide antibiotics, and opioids. Its broad substrate range makes CYP3A4 interactions the most frequently encountered in clinical practice.
What are the CYP2D6 metabolizer phenotypes and why do they matter?
CYP2D6 has four phenotypes: Ultra-rapid Metabolizer (UM, gene duplications), Normal/Extensive Metabolizer (EM), Intermediate Metabolizer (IM), and Poor Metabolizer (PM, *4/*5 alleles). PMs cannot activate Codeine to Morphine (no pain relief) or Tamoxifen to Endoxifen (reduced cancer protection). UMs over-convert Codeine, risking morphine toxicity. Prevalence varies: PM is ~5-10% in Caucasians, ~1% in East Asians.
How do CYP inhibitor strength classifications work?
The FDA classifies CYP inhibitors by their effect on substrate AUC: strong inhibitors cause a >=5-fold increase, moderate inhibitors a 2-5-fold increase, and weak inhibitors a 1.25-2-fold increase. For CYP3A4, strong inhibitors include Ketoconazole, Itraconazole, Clarithromycin, and Ritonavir; moderate includes Erythromycin, Fluconazole, Diltiazem, and Verapamil.
What is the clinical significance of CYP2C19 genotyping for Clopidogrel?
CYP2C19 Poor Metabolizers (*2, *3 alleles, ~15-25% in East Asians) cannot adequately activate the prodrug Clopidogrel, leading to reduced antiplatelet effect and higher cardiovascular event risk. CPIC guidelines recommend alternative antiplatelet agents (Prasugrel, Ticagrelor) for CYP2C19 PMs. Testing is especially important before coronary stent placement.
Why does smoking affect CYP1A2 drug metabolism?
Polycyclic aromatic hydrocarbons (PAHs) in cigarette smoke are potent CYP1A2 inducers, increasing the metabolism of substrates like Clozapine, Olanzapine, Theophylline, and Caffeine. Smokers taking Clozapine may need higher doses. Critically, when patients quit smoking, CYP1A2 induction reverses and drug levels can rise to toxic concentrations, requiring dose reduction.
What pharmacogenomics tests should be ordered before prescribing Warfarin?
Warfarin dosing is guided by CYP2C9 genotype (metabolizes S-warfarin) and VKORC1 genotype (drug target). VKORC1 -1639 AA genotype (common in East Asians, ~90%) requires significantly lower doses (0.5-2 mg/day) compared to GG genotype (5-7 mg/day). CYP2C9 *3/*3 patients need approximately 75% dose reduction. Combined algorithms are available at warfarindosing.org.
How does SLCO1B1 genotyping relate to statin safety?
The SLCO1B1 *5 variant (c.521T>C) reduces OATP1B1 hepatic uptake transporter activity, increasing systemic statin exposure by 2-4 fold. This significantly raises the risk of Simvastatin-induced myopathy and rhabdomyolysis, which is why the FDA restricted Simvastatin 80mg dosing. CPIC recommends SLCO1B1 genotyping to guide statin selection and dosing.
What HLA tests should be performed before prescribing Carbamazepine?
HLA-B*15:02 testing is recommended before Carbamazepine in patients of Southeast Asian descent (8-15% prevalence) due to the risk of Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis (SJS/TEN). HLA-A*31:01 testing is relevant for European-descent patients at risk for DRESS syndrome. The FDA recommends genetic testing before initiating Carbamazepine therapy.