CYP2C19基因多态性对血液病患者伏立康唑血药浓度的影响及血药浓度监测在侵袭性真菌病防治中的价值

OBJECTIVE: To evaluate the effects of CYP2C19 genetic polymorphism on the plasma concentration of voriconazole in patients with hematological disease and the value of serial monitoring plasma concentrations in the treatment and prevention of invasive fungal disease (IFD). METHODS: From January 2016 to December 2016, 65 hematological patients who received voriconazole intravenous administration for the treatment of invasive fungal disease were enrolled in this study. The population CYP2C19 polymorphism of voriconazole were performed using PCR-Pyrosequencing. The trough plasma concentrations of vriconazole (C(trough)) was detected by ultra performance liquid chromatography tandem mass spectrometry. RESULTS: Based on the genotype analysis, 65 subjects were identified as extensive metabolizers' group (30 cases) and poor metabolizers' group (35 cases). The C(trough) of the 65 patients were detected for 169 times totally, and there was a significant difference of C(trough) values between the two groups [0.98(0.38–2.08) mg/L vs 2.19(1.53–4.27) mg/L, z=10.286, P<0.001]. The medium of C(trough) in 65 hematological patients were described. Lack of response to therapy was more frequent in patients with voriconazole levels <1.5 mg/L (50.0%) than in those with voriconazole levels >1.5 mg/L (20.5%) (P=0.052). And the risk of adverse events was more frequent in patients with voriconazole levels >5.5 mg/L (80.0%) than in those with voriconazole levels ≤5.5 mg/L (8.3%) (χ(2)=11.689, P=0.020). CONCLUSION: Patients with CYP2C19 wild-type phenotype are extensive metabolizers, their C(trough) of voriconazole are significantly lower than patients with CYP2C19 non-wild-type phenotype (poor metabolizers). Appropriate concentrations of vriconazole can improve the efficacy and safety during treatment.