Therapeutic drug monitoring of itraconazole and the relevance of pharmacokinetic interactions

A review of the pharmacological aspects of greatest relevance in relation to the monitoring of itraconazole serum levels is presented in this article. The main causes of pharmacokinetic variability, e.g., poor aqueous solubility, the presystemic first-pass effect with the involvement of transporters such as P-glycoprotein, the high extent of metabolism mediated by the CYP450 system and a high probability of pharmacological interactions, are documented and discussed. The pharmacokinetic–pharmacodynamic criteria used to optimise antibiotic therapy, as well as their application to antifungal drugs, are also discussed. Data concerning the breakpoints established for the minimum serum concentrations of itraconazole are included, and the most relevant justifications for drug monitoring are cited.