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

Taotao Wang, Jiao Xie, Yan Wang, Xiaowei Zheng, Jin'e Lei, Xue Wang, Haiyan Dong, Qianting Yang, Limei Chen, Jianfeng Xing, Yalin Dong

Index: Pharmacotherapy 35 , 797-804, (2015)

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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 2 weeks.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 2.31 mg/L, range 1.06-4.01 mg/L), 12-hour area under the plasma concentration-time curve (AUCτ ) (median 21.18 hr mg/L, range 7.71-42.07 hr mg/L), ratio of the unbound drug AUC over 24 hours (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.© 2015 Pharmacotherapy Publications, Inc.