A retrospective study of plasma concentration of voriconazole in leukemia patients

Abstract

Objective 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. Methods 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. Results 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). Conclusion 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. Key words: Voriconazole; Liquid chromatography-mass spectrometry; Gene