title: Triazole antifungal agents drug-drug interactions involving hepatic cytochrome P450.
abstract: BACKGROUND
  Triazole antifungal agents are often prescribed as first-line therapy for candidemia, in non-neutropenic hosts and invasive pulmonary aspergillosis, and in critically ill patients who receive many concomitant medications. As substrates and inhibitors of cytochrome P450 (CYP), the triazoles can interact with many drugs, which may lead to enhanced toxicity of the concomitant medication(s) or ineffective antifungal treatment. Therefore, clinicians must understand the drug interaction profile of this class.
  
  
  METHODS
  This manuscript reviews the role of human hepatic CYP in triazole-drug interactions, illustrates how recent discoveries in pharmacogenetics and triazole metabolism impact our understanding of these interactions, and summarizes the most clinically important triazole-drug interactions. A search of English language, original research and scholarly reviews describing interactions between triazole antifungal agents and human CYP published from 1980 to present was undertaken using PubMed.
  
  
  CONCLUSIONS
  Triazoles interact with many drugs and the primary mechanism for these interactions is hepatic CYP. Many studies published in the past 2 decades characterize these interactions using the state-of-the-art methods of the time. However, advances in genotyping, improved analytical technology and bioanalytical methods, which enable accurate molecular identification and stereochemical analysis, have substantially added to the understanding of the role hepatic CYP plays in triazole-drug interactions in humans.
authors: University of Arkansas for Medical Sciences, College of Pharmacy , Department of Pharmacy Practice, Little Rock, AR 72205, USA. gubbinspaulo@uams.edu
authors: Paul O
authors: PO
authors: Gubbins
mesh_terms: D000935:Antifungal Agents / Q000009:adverse effects / Q000378:metabolism* / Q000627:therapeutic use; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000378:metabolism*; D004347:Drug Interactions; D006801:Humans; D009181:Mycoses / Q000188:drug therapy*; D014230:Triazoles / Q000009:adverse effects / Q000378:metabolism* / Q000627:therapeutic use
chemical_list: D000935:Antifungal Agents; D014230:Triazoles; D003577:Cytochrome P-450 Enzyme System