Voriconazole therapeutic drug monitoring in patients with invasive mycoses improves efficacy and safety outcomes
Voriconazole therapeutic drug monitoring in patients with invasive mycoses improves efficacy and safety outcomes
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DOI：
10.1086/524669
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发表时间：
2008-01-15
影响因子：
11.8
通讯作者：
Marchetti, Oscar
中科院分区：
文献类型：
--
作者：
Pascual, Andres;Calandra, Thierry;Marchetti, Oscar
背景伏立康唑是治疗曲霉病的首选药物，也是治疗念珠菌病的新选择。肝病、年龄、细胞色素CYP2C19遗传多态性和合并用药影响伏立康唑代谢。伏立康唑药代动力学的较大变化可能与疗效降低或毒性有关。本研究旨在评估个体化剂量调整后伏立康唑血药浓度测定的实用性。在52例患者的2388个治疗日期间，共进行了181次高压液相色谱测量。伏立康唑血药谷浓度变异性较大，31%的病例范围为5.5 mg/L（可能与毒性相关的水平）。伏立康唑水平1 mg/L的患者对治疗缺乏反应更常见（39例患者中有15例[12%]; P =.02）。增加伏立康唑剂量后，血药浓度> 1 mg/L，所有6例患者的感染均完全消退。在16例伏立康唑谷血药浓度> 5.5 mg/L的患者中，5例（31%）出现脑病，包括4例接受静脉给药的患者，伏立康唑的中位剂量为8 mg/kg/d，而伏立康唑谷血药浓度> 5.5 mg/L的患者中无一例出现脑病。
Background. Voriconazole is the therapy of choice for aspergillosis and a new treatment option for candidiasis. Liver disease, age, genetic polymorphism of the cytochrome CYP2C19, and comedications influence voriconazole metabolism. Large variations in voriconazole pharmacokinetics may be associated with decreased efficacy or with toxicity.Methods. This study was conducted to assess the utility of measuring voriconazole blood levels with individualized dose adjustments.Results. A total of 181 measurements with high-pressure liquid chromatography were performed during 2388 treatment days in 52 patients. A large variability in voriconazole trough blood levels was observed, ranging from 5.5 mg/L (a level possibly associated with toxicity) in 31% of cases. Lack of response to therapy was more frequent in patients with voriconazole levels 1 mg/L (15 [12%] of 39 patients; (P = .02). Blood levels >1 mg/L were reached after increasing the voriconazole dosage, with complete resolution of infection in all 6 cases. Among 16 patients with voriconazole trough blood levels >5.5 mg/L, 5 patients (31%) presented with an encephalopathy, including 4 patients who were treated intravenously with a median voriconazole dosage of 8 mg/kg per day, whereas none of the patients with levels