1. Pharmacokinetic and Pharmacodynamic Properties of Oral Voriconazole in Patients with Invasive Fungal Infections.
- Author
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Wang, Taotao, Xie, Jiao, Wang, Yan, Zheng, Xiaowei, Lei, Jin'e, Wang, Xue, Dong, Haiyan, Yang, Qianting, Chen, Limei, Xing, Jianfeng, and Dong, Yalin
- Subjects
PHARMACOKINETICS ,PHARMACODYNAMICS ,MYCOSES ,VORICONAZOLE ,THERAPEUTICS - Abstract
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 ( IFIs). Design Prospective and observational PK/ PD study. Setting A university-affiliated medical center. Patients Fifteen hospitalized patients with proven IFIs 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 ( 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 ( R2 = 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; χ2 = 1.61, p=0.688). Conclusion 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. [ABSTRACT FROM AUTHOR]- Published
- 2015
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