Analysis of High Variability of Voriconazole Trough Concentration in Patients with Haematological Malignancies

OBJECTIVE To explore the potential factors associated with the variability of voriconazole trough concentration in patients with haematological malignancies. METHODS Medical history, clinical data, medication status and laboratory data of patients with haematological malignancies who underwent voriconazole therapeutic drug monitoring were retrospectively collected from November 2015 to September 2017. The correlation between normalized trough concentrations and demographics, physiological and pathology, drug combination, and CYP2C19 genotype was analyzed. RESULTS A total of 176 patients, 241 cases of monitoring data were included in the study. The results showed that voriconazole trough concentration in patients with haematological malignancies had high variability. Univariate and multivariate Logistic analysis suggested the CYP2C19*1/*1(extensive metabolizer) increased the risk of normalized trough concentration <1.0 mg·L^-1(OR:4.445, 95%CI:1.514-38.449, P=0.015); While C-reactive protein(OR:2.377, 95%CI:1.116-5.063, P=0.025), combined with omeprazole(OR:4.537, 95%CI:1.716-14.637, P=0.018), and CYP2C19*2/*2, *2/*3 and *3/*3 (poor metabolizer)(OR:10.199, 95%CI:2.516-21.342, P=0.001) were risk factors of normalized trough concentration >5.5 mg·L^-1. CONCLUSION Voriconazole trough concentration in patients with haematological malignancies has high variability and complicated factor. CYP2C19 genotype, concomitant with omeprazole, and inflammation should be considered in the treatment.