Department of Pharmacy, Kitasato University East Hospital, 2-1-1, Asamizodai, Minamiku, Sagamihara, Kanagawa, 258-0380, Japan.
J Infect Chemother. 2012 Aug;18(4):501-7. doi: 10.1007/s10156-011-0363-6. Epub 2012 Jan 11.
Voriconazole (VRCZ) reportedly possesses a broad spectrum of antifungal activity against Aspergillus spp. and Candida spp., and the blood concentration of VRCZ is correlated with both the efficacy and the adverse effects of this drug. Monitoring of the blood concentration target level of VRCZ has not yet been widely adopted in the medical field, and no evidence concerning this target level has been reported. Accordingly, we used a meta-analysis to investigate the optimal blood concentration of VRCZ. Using data from 12 reports, we found that the success rate for fungal infection treatment increased significantly at VRCZ levels greater than 1.0 μg/ml when a graded cutoff value within the range of 1.0-3.0 μg/ml was used as the VRCZ trough blood concentration [odds ratio (OR) 7.23, 95% confidence interval (CI) 2.84-18.37, P < 0.0001]. Concerning the safety evaluation, the incidence of adverse neurological effects increased significantly at a cutoff value of 4.0 μg/ml when a graded cutoff value within the range of 3.0-6.0 μg/ml was used (OR 2.23, 95% CI 1.12-4.46, P = 0.02). However, in all 12 literature sources, an increasing incidence of liver dysfunction was reported at higher blood concentrations, and no accurate cutoff values were obtained. Consequently, a VRCZ trough blood concentration more than 1.0 μg/ml from the perspective of efficacy and less than 4.0 μg/ml from the perspective of safety is recommended.
报道称伏立康唑（VRCZ）对曲霉菌属和念珠菌属具有广谱抗真菌活性，VRCZ 的血药浓度与该药物的疗效和不良反应均相关。VRCZ 的血药浓度靶目标水平尚未在医学领域广泛采用，也没有关于该靶目标水平的证据。因此，我们使用荟萃分析来研究 VRCZ 的最佳血药浓度。使用来自 12 份报告的数据，我们发现当使用 1.0-3.0μg/ml 范围内的分级截止值作为 VRCZ 谷浓度时，VRCZ 水平大于 1.0μg/ml 时真菌感染治疗的成功率显著提高[比值比（OR）7.23，95%置信区间（CI）2.84-18.37，P<0.0001]。关于安全性评估，当使用 3.0-6.0μg/ml 范围内的分级截止值时，4.0μg/ml 的截止值显著增加了不良神经效应的发生率（OR 2.23，95%CI 1.12-4.46，P=0.02）。然而，在所有 12 篇文献中，均报告了随着血药浓度升高，肝功能障碍的发生率增加，但没有获得准确的截止值。因此，建议从疗效角度来看，VRCZ 的谷浓度应大于 1.0μg/ml，从安全性角度来看，VRCZ 的谷浓度应小于 4.0μg/ml。
