Niveau de preuve du suivi thérapeutique pharmacologique du voriconazole

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-dependant renal deficiency or hepatic insufficiency, cystic fibrosis patients or those treated concomitantly with interfering drugs. According to our survey, herapeutic drug monitoring of voriconazole appearsrecommended. However, controlled studies are still necessary to validate it prospectively and to evaluate pharmacokinetically-based methods proposed for individual dose adjustment.