伏立康唑血药浓度监测及其影响因素分析

目的：讨论伏立康唑体内血药浓度个体差异大的影响机制，为临床合理使用伏立康唑提供依据。方法：回顾性分析109名使用伏立康唑的患者，分析其CYP2C19基因型，测定血中伏立康唑及其主要代谢物浓度，统计分析性别，年龄，溶媒，CYP2C19基因型、C反应蛋白，药物相互作用对伏立康唑血药浓度的影响，并统计分析使用伏立康唑前后肝酶指标的情况。结果：性别、年龄及临床常用溶媒对伏立康唑血药浓度无显著性影响；不同基因型之间，伏立康唑血药浓度及代谢物浓度之间无显著性差异，代谢率（代谢物浓度与原药浓度比值）有显著性差异；随着C反应蛋白增加，伏立康唑浓度升高，并在<40，40~200、>200组间具有显著性差异。质子泵抑制剂能显著性影响伏立康唑浓度，其他利尿剂、激素对伏立康唑血药浓度无显著性差异。结论：伏立康唑血药浓度受影响因素较多，对于临床重症患者更应该加强血药浓度监测。

Retrospective of voriconazole therapeutic drug monitoring

OBJECTIVE To assess clinical factors and drug interactions that may affect the mechanism of the variability of voriconazole plasma concentration.METHODS Medical records were reviewed for patients who received voriconazole and had at least 1 concentration measured. The study included 109 patients with 125 voriconazole trough concentrations. Relationship of multiple factors including sex, age, vehicle, CYP2C19, drug combination and the level of C-reaction protein were identified. Furthermore, liver functions were assessed before and after the therapy.RESULTS The results showed that with the increase of CRP, the trough concentration increased. There was no statistical significance in the interaction between sex, enzyme or drug. Determination of voriconazole metabolites in human plasma by ultra fast liquid chromatography tandem mass spectrometry method, determination of CYP2C19 genotype, analysis of the influence of genotype on blood concentration, showed no statistical significance, but metabolic rate was significant.CONCLUSION Voriconazole therapeutic drug levels are variable and can be affected by several factors such as co-administrated with PPI as well as inflammation.