Pharmacokinetic-pharmacodynamic study of itraconazole in patients with fungal infections in intensive care units

Severely ill patients in intensive care units (ICU) are frequently at risk of developing fungal infections. Itraconazole (ITCZ), a triazole antifungal agent, is used for the treatment of aspergillosis, candidiasis, and cryptoccosis. The present retrospective pharmacokinetic-pharmacodynamic (PK-PD) analysis was designed to find any factors affecting clinical outcome of ITCZ treatment, and was performed to evaluate the appropriateness of the current dosage regimen in ICU patients. All of the patients admitted to Aichi Medical University Hospital ICU in 2008 who were treated with ITCZ injections for fungal infections were included in the study. After outcomes had been classified as cure or failure, a PK-PD analysis was performed. In addition, the probability of PD target attainment was assessed using a Monte Carlo simulation. Ten patients were enrolled in the study. Satisfactory outcomes were obtained in 4 of the 10 patients. No significant differences in the area under the 24-h curve (AUC(0-24)), peak concentrations and trough concentrations were observed between the two groups. However, it was observed that the higher the AUC(0-24), the better the outcome. Moreover, our results showed that additional dosage is needed to attain a sufficiently high AUC(0-24)/MIC in about 20% of patients. Our retrospective study is the first to show that it is important to consider the host's condition when ITCZ is administered, especially in ICU patients. The present findings are also useful for optimizing the individual dosage of ITCZ based on AUC(0-4) for the treatment of patients infected with Candida spp.