Metabolism

Cytochrome P-450 3A3/4 Isoenzyme

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

  • 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
  • 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)
  • 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. Erythromycin
    8. Telithromycin (Ketek)
    9. Clarithromycin
      1. Serious risk of Hypotension and Acute Kidney Injury when combined with Calcium Channel Blocker
      2. Gandhi (2013) JAMA 310(23):2544-53 [PubMed]
  4. Miscellaneous
    1. Bromocriptine
    2. Cimetidine
    3. Estrogens (Ethinyl Estradiol)
    4. Grapefruit juice
    5. Mibefradil
    6. Omeprazole (Prilosec)
  • 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