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Cytochrome P-450 3A3/4 IsoenzymeAka: Cytochrome P-450 3A3, Cytochrome P-450 3A4, CYP3A3, CYP3A4, CYP3As

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  1. Background
    1. Responsible for majority of P-450 drug interactions
    2. Accounts for 40 to 60% of hepatic P-450 isoenzymes
    3. Also present in intestinal epithelium
  2. Interactions: Metabolized by CYP 3A3/4 (Substrates)
    1. Neuropsychiatric drugs
      1. Anticonvulsants
        1. Carbamazepine (Tegretol)
        2. Ethosuximide (Zarontin)
      2. Tertiary amine Tricyclic Antidepressants
        1. Amitriptyline (Elavil)
        2. Clomipramine
        3. Imipramine
      3. Antipsychotics
        1. Clozapine
      4. Benzodiazepines
        1. Alprazolam (Xanax)
        2. Diazepam (Valium)
        3. Midazolam (Versed)
        4. Triazolam (Halcion)
      5. Other
        1. Ergotamine: Inhibitor
    2. Cardiopulmonary Drugs
      1. Antiarrhythmics
        1. Amiodarone (Cordarone)
        2. Disopyramide (Norpace)
        3. Lidocaine (Xylocaine)
        4. Propafenone (Rythmol)
        5. Quinidine
      2. Lipid lowering agents (i.e. Statins)
        1. Lovastatin (Mevacor)
        2. Simvastatin (Zocor)
        3. Atorvastatin (Lipitor)
        4. Cerivastatin
      3. Antihypertensives
        1. Felodipine (Plendil)
        2. Diltiazem (Cardizem)
        3. Nifedipine (Procardia, Adalat)
        4. Verapamil (Calan)
        5. Amlodipine (Norvasc)
        6. Nisoldipine
        7. Nimodipine (Nimotop)
    3. Antibiotics
      1. Macrolide antibiotics
        1. Clarithromycin
        2. Troleandomycin
      2. HIV Protease Inhibitors
        1. Indinavir
        2. Nelfinavir
        3. Ritonavir
        4. Saquinavir
        5. Amprenavir
    4. Miscellaneous
      1. Alfentanil
      2. Cisapride (Propulsid)
      3. Estrogens (Ethinyl Estradiol, 17 B-estradiol)
      4. Opioids
        1. Codeine
        2. Alfentanil
        3. Fentanyl
        4. Sufentanil
      5. Sildenafil (Viagra)
      6. Testosterone
      7. Tamoxifen
      8. Vincristine
      9. Vinblastine
      10. Ifosfamide
      11. Cyclophosphamide
      12. Astemizole (Hismanal)
      13. Terfenadine (Seldane)
      14. Loratadine (Claritin)
      15. Cyclosporine
      16. Tacrolimus
      17. Zolpidem (Ambien)
      18. Corticosteroids (Budesonide, Cortisol)
  3. Interactions: Inhibitor of CYP 3A3/4
    1. Neuropsychiatric drugs
      1. Midazolam (Versed)
      2. Nefazodone (Serzone)
    2. Cardiopulmonary Drugs
      1. Quinidine
      2. Diltiazem (Cardizem)
      3. Nifedipine (Procardia, Adalat)
      4. Verapamil (Calan)
      5. Zafirlukast
    3. Antibiotics
      1. Indinavir
      2. Nelfinavir
      3. Ritonavir
      4. Fluconazole
      5. Itraconazole
      6. Ketoconazole
      7. Clarithromycin
      8. Erythromycin
      9. Telithromycin (Ketek)
    4. Miscellaneous
      1. Bromocriptine
      2. Cimetidine
      3. Estrogens (Ethinyl Estradiol)
      4. Grapefruit juice
      5. Mibefradil
      6. Omeprazole (Prilosec)
  4. Interactions: Inducer of CYP 3A3/4
    1. Neuropsychiatric drugs
      1. Carbamazepine
      2. Phenobarbital and other barbiturates
      3. Phenytoin
      4. Hypericum perforatum (St. John's Wort)
    2. Antibiotics
      1. Rifampin
    3. Miscellaneous
      1. Dexamethasone
      2. Troglitazone

Cytochrome P450 3A4 (C1142644)

Definition (NCI)Induced primarily in liver by glucocorticoids, drugs, pesticides, and carcinogens and encoded by human CYP3A4 Gene (Cytochrome P450 IIIA Subfamily), Cytochrome P450 3A4 is a 502-amino acid 57.3-kD membrane-bound ER heme-thiolate monooxygenase. CYP3A4 is involved in an NADPH-dependent electron transport pathway and phase I oxidative metabolism of carcinogens, steroids, fatty acids, and xenobiotics, as well as bioactivation of aflatoxin B(1) to a genotoxic derivative. Activity seems a key predictor of drug responsiveness and toxicity. (from LocusLink, Swiss-Prot, OMIM, and NCI)
ConceptsAmino Acid, Peptide, or Protein (T116) , Enzyme (T126)
EnglishCYP3A4, cyt P450 3A4, cytochrome P-450 3A4, Cytochrome P450 3A4, Cytochrome p450 CYP3A4 enzyme, Cytochrome P450 Nifedipine Oxidase, Cytochrome P450PCN1, EC 1.14.14.1, Glucocorticoid-Inducible P450, Nifedipine Oxidase, P450 3A4, P450-3A4, Quinine 3-Monooxygenase, Steroid-Inducible P450- III
Spanishenzima CYP3A4 del citocromo p450
Parent ConceptsCytochrome P450 (C0010762), cytochrome P450 3A (C0059563)
SourcesMSH, MTH, NCI, SCTSPA, SNOMEDCT
Derived from the NIH UMLS (Unified Medical Language System)


CYP3A4 wt Allele (C1705261)

Definition (NCI)Human CYP3A4 wild-type allele is located in the vicinity of 7q21.1 and is approximately 27 kb in length. This allele, which encodes cytochrome P450 3A4 protein, plays a role in the oxidation of steroids, drugs, carcinogens and other xenobiotics. CYP3A4 gene dysfunction is associated with both lung cancer and epipodophyllotoxin-induced leukemogenesis.
ConceptsGene or Genome (T028)
EnglishCP33, CP34, CYP3, CYP3A, CYP3A3, CYP3A4 wt Allele, CYPIIIA4, HLP, NF-25, P450-PCN1, P450C3, P450PCN1
Parent ConceptsCYP3A4 gene (C1176140)
SourcesMTH, NCI
Derived from the NIH UMLS (Unified Medical Language System)



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