title: [Level of evidence for therapeutic drug monitoring of voriconazole].
abstract: Voriconazole is a major antifungal drug with activity against endemic fungi, Candida and Aspergillus species in immunocompromised patients. Voriconazole has a good bioavailability, an high protein binding percentage in plasma and is metabolized in liver via CYP2C19. It presents important neuro- and hepatotoxicities. Some studies determined trough concentrations of voriconazole in plasma using liquid chromatography coupled with UV or tandem mass detection. These studies showed a relationship between trough concentrations of voriconazole and efficacy or toxicity. Indeed, some studies reported a relationship between a lack of clinical response and concentrations below 1 or 2 μg/mL according to the localization of infection, while toxicities are frequently observed at concentrations above 5 μg/mL. Some particular populations will have to be taken into account such as children, patients with hemodialysis-dependent renal deficiency or hepatic insufficiency, cystic fibrosis patients or those treated concomitantly with interfering drugs. According to our survey, therapeutic drug monitoring of voriconazole appears recommended. However, controlled studies are still necessary to validate it prospectively and to evaluate pharmacokinetically-based methods proposed for individual dose adjustment.
authors.affiliation: CHU Henri Mondor, Université Paris XII, Créteil, France. anne.hulin@hmn.aphp.fr
authors.forename: Anne
authors.initials: A
authors.lastname: Hulin
authors.forename: Eric
authors.initials: E
authors.lastname: Dailly
authors.forename: Chantal
authors.initials: C
authors.lastname: Le Guellec
mesh_terms: D000935:Antifungal Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000191:economics / Q000493:pharmacokinetics / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D016903:Drug Monitoring; D019317:Evidence-Based Medicine; D006801:Humans; D009181:Mycoses / Q000188:drug therapy* / Q000382:microbiology; D011743:Pyrimidines / Q000008:administration & dosage / Q000009:adverse effects / Q000191:economics / Q000493:pharmacokinetics / Q000627:therapeutic use*; D014230:Triazoles / Q000008:administration & dosage / Q000009:adverse effects / Q000191:economics / Q000493:pharmacokinetics / Q000627:therapeutic use*; D065819:Voriconazole
chemical_list: D000935:Antifungal Agents; D011743:Pyrimidines; D014230:Triazoles; D065819:Voriconazole