探讨白血病患者伏立康唑血药浓度、基因代谢型及G、GM实验结果的关联性。

建立测定伏立康唑血药浓度的高效液相色谱串联质谱法（HPLC-MS/MS），并利用MATLAB软件对所测血药浓度进行分析，开展G、GM实验，采用t检验比较2种实验结果为阳性和阴性的患者伏立康唑的血药浓度值；使用DNA序列测定法检测CYP2C19*2和CYP2C9*3基因代谢型并探讨其与伏立康唑血药浓度的关联性。

所有患者伏立康唑血药浓度的平均值为（1.47±1.35）μg/ml，伏立康唑在白血病患者中的有效血药浓度为0.44~2.49 μg/ml；G、GM实验阳性的患者伏立康唑血药浓度均小于G、GM实验阴性的患者［（1.32±1.21）μg/ml vs（2.25±1.20）μg/ml；（1.27±0.92）μg/ml vs（2.15±0.81）μg/ml］，且差异具有统计学意义（t=-2.941，P=0.032；t=-12.674，P=0.001）；CYP2C19*2基因代谢型杂合弱代谢基因型GA的血药浓度值高于野生型正常代谢型GG［（1.42±1.13）μg/ml vs（1.30±1.40）μg/ml］，但差异无统计学意义（t=-1.689，P=0.129）；CYP2C9*3基因代谢型杂合弱代谢基因型AC的血药浓度值高于野生型正常代谢型AA［（2.30±2.05）μg/ml vs（1.43±1.15）μg/ml］，差异具有统计学意义（t=12.386，P=0.006）。

白血病患者伏立康唑血药浓度、基因代谢型及G、GM实验阳性存在一定的关联性即患者伏立康唑弱代谢基因型，伏立康唑血药浓度高；患者G、GM实验阳性，伏立康唑血药浓度低。

To analyze the correlation of plasma concentration of voriconazole with the genotype of drug metabolism genes and (1–3)-β-D glucan (G) and glactomannan (GM) tests in leukemia patients to provide a reference for rational clinical application of voriconazole.

Plasma concentration of voriconazole was determined using high performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS) and software MATLAB software. G and GM tests were used to detect fungal infection and to explore whether fungal infection was correlated with the concentration of voriconazole. CYP2C19*2 and CYP2C9*3 genes were genotypes using DNA sequence metabotropic assays to explore whether the genotype was correlated with the concentration of voriconazole.

The mean plasma concentration of voriconazole determined by HPLC-MS/MS analysis was (1.47±1.35) μg/mL, and the range of the effective concentration was 0.44-2.49 μg/mL. The concentration of voriconazole in the G/GM test-positive group was significantly lower than that in the negative group [(1.32±1.21) μg/ml vs (2.25±1.20) μg/ml; (1.27±0.92) μg/ml vs (2.15±0.81) μg/ml], the difference is statistically significant (t=-2.941, P=0.032; t=-12.674, P=0.001). The concentration of voriconazole in the CYP2C19*2(GA) group was greater than that in the CYP2C19*2(GG) [(1.42±1.13) μg/ml vs (1.30±1.40) μg/ml], but there was no significant difference (t=-1.689, P=0.129). The concentration of voriconazole in the CYP2C9*3(AC) group was significantly greater than that in the CYP2C9*3(AA) group (t=12.386, P=0.006).

The concentration of voriconazole correlates with the genotype of CYP2C19*2 and CYP2C9*3 genes and G and GM tests in leukemia patients. The concentration of voriconazole is high in patients with voriconazole weakly metabolized genotype, and is low in patients with positive G and GM tests.