Impact of inflammation and concomitant glucocorticoid administration on plasma concentration of triazole antifungals in immunocompromised patients.

Background: The expression of hepatic CYP3A decreases with inflammatory response but increases with glucocorticoid administration. The aim of this study was to evaluate the plasma concentration of voriconazole and itraconazole under inflammatory conditions and glucocorticoid therapy.

Methods: Forty-one voriconazole- and 42 itraconazole-treated immunocompromised patients were enrolled in this study. Plasma concentrations of triazoles and their major metabolites at 12h after dosing were determined. The relationships between C-reactive protein (CRP), prednisolone dose, and plasma exposure parameters of triazole were evaluated.

Results: Plasma concentration of voriconazole was not correlated with that of its N-oxide. A higher CRP was correlated with a higher dose-normalized plasma concentration of voriconazole and a lower plasma concentration ratio of N-oxide to voriconazole. Prednisolone dose was weakly correlated with the plasma concentration ratio of N-oxide to voriconazole. Plasma concentration of itraconazole had a good correlation with that of its hydroxide. Parameters of itraconazole were not associated with CRP and prednisolone dose.

Conclusions: An inflammatory state raised the plasma concentration of voriconazole through its metabolic reduction, while it did not have an effect on plasma concentration of itraconazole. Concomitant glucocorticoid administration slightly elevated the voriconazole metabolism, although it did not affect the plasma concentration of triazoles.