Pharmacokinetic and Pharmacodynamic Properties of Oral Voriconazole in Patients with Invasive Fungal Infections.

Abstract

To assess the pharmacokinetic and pharmacodynamic (PK/PD) properties of voriconazole and to investigate the relationship between PK/PD parameters and the efficacy of a fixed-dose oral regimen in the treatment of invasive fungal infections (IFIs). Prospective and observational PK/PD study. A university-affiliated medical center. Fifteen hospitalized patients with proven IFIs who were treated with oral voriconazole for at least 2weeks. We investigated the PK/PD properties of voriconazole using a noncompartmental analysis in 15 patients. Marked interpatient variation in voriconazole pharmacokinetic properties was noted including peak plasma concentrations (median 2.31mg/L, range 1.06-4.01mg/L), 12-hour area under the plasma concentration-time curve (AUCτ ) (median 21.18hrmg/L, range 7.71-42.07hrmg/L), ratio of the unbound drug AUC over 24hours (fAUC24 ) divided by the minimum inhibitory concentration (fAUC24 :MIC; median 62.61, range 6.48-415.30), and the free trough plasma concentration (Cmin ) divided by the MIC (fCmin :MIC; median 1.81, range 0.46-15.52). There was a good correlation between voriconazole Cmin and AUCτ (R(2) =0.805). Voriconazole therapy was effective in 66.7% of patients (10/15). No significant difference was observed with regard to successful clinical response between the patients with a fAUC24 :MIC and fCmin :MIC values higher than 25 and higher than 1 (10/12 vs 10/13, respectively; χ(2) =1.61, p=0.688). There is substantial interpatient variability in the PK/PD properties of voriconazole. fAUC24 :MIC values higher than 25 and fCmin :MIC values higher than 1 may predict clinical response in patients with IFIs. Designing an optimal dosage regimen based on individual PK/PD properties will improve the efficacy in patients with IFIs.