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Optimization of voriconazole dosage regimen to improve the efficacy in patients with invasive fungal disease by pharmacokinetic/pharmacodynamic analysis
Author(s) -
Chen Lu,
Wang Taotao,
Wang Yan,
Yang Qianting,
Xie Jiao,
Li Ying,
Lei Jin'e,
Wang Xue,
Xing Jianfeng,
Dong Yalin,
Dong Haiyan
Publication year - 2016
Publication title -
fundamental and clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.655
H-Index - 73
eISSN - 1472-8206
pISSN - 0767-3981
DOI - 10.1111/fcp.12212
Subject(s) - voriconazole , cmin , medicine , regimen , pharmacokinetics , pharmacodynamics , dosing , pharmacology , cmax , antifungal , dermatology
Invasive fungal disease ( IFD ) is a significant cause of morbidity and mortality in hospitalized patients. To maximize the efficacy of voriconazole treatment, the study established the relationship between voriconazole pharmacokinetic/pharmacodynamic ( PK / PD ) and probability of response and optimized voriconazole dosage regimen in patients with IFD based on Monte Carlo simulation. Forty‐four patients proven with IFD were involved in this study. Among them, the overall cure rate was 75% (33/44) and there was a significant difference between C min / MIC values in patients with lack of response ( n = 11) and those with successful response ( n = 33) (mean value: 1.91 vs. 11.33; P < 0.05). Logistic regression model showed a high correlation between voriconazole C min / MIC ratio and clinical response ( P = 0.044, OR = 1.349). According to Monte Carlo simulation results under different voriconazole dosing regimens, we could draw a conclusion that 200 mg voriconazole administered intravenously or orally twice daily for Candida infections and 300 mg administered orally or with 200 mg administered intravenously twice daily for Aspergillus infections were rational, which could achieve a value of the cumulative fraction of response >90%. This study built the relationship between voriconazole PK / PD and clinical response and obtained the reasonable empirical dosage regimen, which can be used to customize individual dosage regimen and improve the efficacy of voriconazole treatment.