Bioanalytical methods for the determination of itraconazole and hydroxyitraconazole: overview from clinical pharmacology, pharmacokinetic, pharmacodynamic and metabolism perspectives.

Itraconazole represents an important therapeutic option for the treatment of fungal infections. Itraconazole undergoes rapid metabolism to form hydroxyitraconazole, which also contributes to the anti-fungal activity exhibited by the parent compound. Since both itraconazole and hydroxyitraconazole are effective inhibitors of cytochrome P450 (CYP) 3A4 and p-glycoprotein (pgp)-mediated efflux transporters, they have the potential to elicit drug-drug interaction with a number of CYP3A4 and/or pgp substrates. This review focuses on providing comprehensive details on the bioanalytical methods available for the quantitation of both itraconazole and hydroxyitraconazole. Additionally, it provides an overview of the clinical pharmacology (several case studies of drug-drug interactions), pharmacokinetics, pharmacodynamics and metabolism related aspects of itraconazole.