title: [Cytochrome P-450 3A4--the most important arena for drug interactions in the body].
abstract: BACKGROUND
  Drug metabolism is often dependent on the cytochrome P-450 enzyme CYP3A4. Some drugs are powerful inhibitors of CYP3A4, whereas others are inducers. Thus, numerous drug interactions are caused by altered CYP3A4 enzyme activity.
  
  
  METHODS
  Based on our own continuous work with drug interactions during the last 10 - 15 years, we here present an overview of the most important CYP3A4 interactions and suggestions on how to handle them in clinical practice.
  
  
  RESULTS
  The combination of a drug being a powerful inhibitor of CYP3A4 and a drug dependent on CYP3A4 for its metabolism may increase the plasma levels of the substrate as much as 10 to 20-fold, with adverse drug reactions and toxic effects as a result. Correspondingly, a combination with an inducer may cause a decrease in the plasma level of the substrate to only 5 - 10 % of its original concentration, leading to therapeutic failure.
  
  
  CONCLUSIONS
  One should avoid drug combinations that cause such profound changes in substrate plasma levels as those described above. With smaller changes in plasma levels an alternative is to combine dose adjustments with frequent clinical controls.
authors.affiliation: Avdeling for klinisk farmakologi St. Olavs Hospital 7006 Trondheim og Institutt for laboratoriemedisin, barne- og kvinnesykdommer Norges teknisk-naturvitenskapelige universitet. olav.spigset@legemidler.no
authors.forename: Olav
authors.initials: O
authors.lastname: Spigset
authors.forename: Espen
authors.initials: E
authors.lastname: Molden
mesh_terms: D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood; D000927:Anticonvulsants / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood; D000935:Antifungal Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood; D002317:Cardiovascular Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood; D051544:Cytochrome P-450 CYP3A / Q000096:biosynthesis / Q000378:metabolism*; D065692:Cytochrome P-450 CYP3A Inhibitors; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D006801:Humans
chemical_list: D000900:Anti-Bacterial Agents; D019380:Anti-HIV Agents; D000927:Anticonvulsants; D000935:Antifungal Agents; D002317:Cardiovascular Agents; D065692:Cytochrome P-450 CYP3A Inhibitors; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human