CYP3A4: The Workhorse

  • Jennifer DeCou
  • Nathaniel Birgenheier
  • Randal O. Dull

Abstract

This chapter discusses the genetics, metabolic actions, substrates, inducers, and inhibitors of cytochrome P450 3A4.

Keywords

Cytochrome P450 CYP P450 3A4 CYP3A4 Pharmacokinetic Metabolism Metabolic pathway Enzyme Induction Inhibitor Substrate Oxidase Mixed-function oxidase Liver Intestine Hepatocytes Enterocytes Chromosome Gene locus 7q21.3-7q22.1 MDR gene Multi-drug resistance P-glycoprotein Pregname X receptor PXR receptor Constitutive androstane receptor CAR receptor Vitamin D Vitamin D response Polymorphism Aliphatic oxidation Aromatic hydroxylation N-dealkylation O-demethylation Oxidative deamination Sulfoxide formation N-hydroxylation Felodipine Tertiary amine tricyclic anti-depressants Antipsychotics Macrolide antibiotics Dihydropyridine calcium-channel blockers HMG CoA reductase inhibitors Statins Carbamazepine Steroid compounds Protease inhibitors Ritonavir Anticonvulsants Rifampin St. John’s Wort SSRI’s Quinolone antibiotics Azole antifungals Grapefruit juices Bergamottin Dihydroxybergamottin Torsade de pointes Rhabdomyolysis Midazolam Rifampin Intraconazole Midazolam Ketamine Fentanyl Alfentanil Sufentanil Methadone Local anesthetics Lidocaine Bupivacaine Ketamine Methadone 

References

  1. 1.
    Dresser GK, Spence JD, et al. Pharmacokinetic-pharmacodynamic consequences and clinical relevance of cytochrome P450 3A4 inhibition. Clin Pharmacokinet. 2000;38(1):41–57.PubMedCrossRefGoogle Scholar
  2. 2.
    Pal D, Mitra AK. MDR- and CYP3A4-mediated drug-herbal interactions. Life Sci. 2006;78(18):2131–45.PubMedCrossRefGoogle Scholar
  3. 3.
    Ohno Y, Hisaka A, et al. General framework for the quantitative prediction of CYP3A4-mediated oral drug interactions based on the AUC increase by coadministration of standard drugs. Clin Pharmacokinet. 2007;46(8):681–96.PubMedCrossRefGoogle Scholar
  4. 4.
    Paine MF, Khalighi M, Fisher JM, et al. Characterization of interintestinal and intraintestinal variations in human CYP3A-dependent metabolism. J Phamacol Exp Ther. 1997;283:1552–62.Google Scholar
  5. 5.
    Sandson NB. Drug-Drug Interaction Primer: A Compendium of Case Vignettes for the Practicing Clinician. Washington DC: American Psychiatric Publishing, Inc; 2007.Google Scholar
  6. 6.
    Ketter TA, Flockhart DA, Post RM, et al. The emerging role of cytochrome P4503A in psychopharmacology. J Clin Psychopharmacol. 1995;15:387–8.PubMedCrossRefGoogle Scholar
  7. 7.
    Monahan BP, Ferguson CL, Killeavy ES, et al. Torsades de pointes occurring in association with terfenadine use. JAMA. 1990;264:2788–90.PubMedCrossRefGoogle Scholar
  8. 8.
    Tsai WC, Tsai LM, Chen JH. Combined use of astemizole and ketoconazole resulting in Torsades de pointes. J Formos Med Assoc. 1997;96:144–6.PubMedGoogle Scholar
  9. 9.
    Ayanian JZ, Fuchs CS, Stone RM. Lovastatin and rhabdomyolysis (letter). Ann Intern Med. 1988;109:682–3.PubMedCrossRefGoogle Scholar
  10. 10.
    Corpier CL, Jones PH, Suki WN, et al. Rhabdomyolysis and renal injury with lovastatin use: report of two cases in cardiac transplant recipients. JAMA. 1988;260:239–41.PubMedCrossRefGoogle Scholar
  11. 11.
    Biesenbach G, Janko O, Stuby U, et al. Myoglobinuric renal failure due to long-standing lovastatin therapy in a patient with pre-existing chronic renal insufficiency. Nephrol Dial Transplant. 1996;11:2059–60.PubMedCrossRefGoogle Scholar
  12. 12.
    Hino I, Akama H, Furuya T, et al. Pravastatin-induced rhabdomyolysis in a patient with mixed connective tissue disease. Arthritis Rheum. 1996;39:1259–60.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • Jennifer DeCou
    • 1
  • Nathaniel Birgenheier
    • 1
  • Randal O. Dull
    • 2
  1. 1.Department of AnesthesiologyUniversity of Utah School of MedicineSalt Lake CityUSA
  2. 2.Department of AnesthesiologyUniversity of Illinois at ChicagoChicagoUSA

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