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

Study Objectives 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 ( IFI s). Design Prospective and observational PK / PD study. Setting A university‐affiliated medical center. Patients Fifteen hospitalized patients with proven IFI s who were treated with oral voriconazole for at least 2 weeks. Methods We investigated the PK / PD properties of voriconazole using a noncompartmental analysis in 15 patients. Results Marked interpatient variation in voriconazole pharmacokinetic properties was noted including peak plasma concentrations (median 2.31 mg/L, range 1.06–4.01 mg/L), 12‐hour area under the plasma concentration‐time curve ( AUC τ ) (median 21.18 hr mg/L, range 7.71–42.07 hr mg/L), ratio of the unbound drug AUC over 24 hours ( f AUC 24 ) divided by the minimum inhibitory concentration ( f AUC 24 : MIC ; median 62.61, range 6.48–415.30), and the free trough plasma concentration (C min ) divided by the MIC ( f C min : MIC ; median 1.81, range 0.46–15.52). There was a good correlation between voriconazole C min and AUC τ ( 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 f AUC 24 : MIC and f C min : MIC values higher than 25 and higher than 1 (10/12 vs 10/13, respectively; χ 2  = 1.61, p=0.688). Conclusion There is substantial interpatient variability in the PK / PD properties of voriconazole. f AUC 24 : MIC values higher than 25 and f C min : MIC values higher than 1 may predict clinical response in patients with IFI s. Designing an optimal dosage regimen based on individual PK / PD properties will improve the efficacy in patients with IFI s.