Effect of CYP2C19 polymorphism on Voriconazole Cmin in children with hematological malignancies complicated with invasive fungal infection

Objective To explore the effect of CYP2C19 polymorphism on plasma minimum concentration of Voriconazole in children with hematological malignancies complicated with invasive fungal infection. Methods Twenty children with hematological malignancies complicated with invasive fungal infection were selected from the Department of Pediatrics, the First Affiliated Hospital of Zhengzhou University were selected, and 5 mL venous blood for each was extracted.CYP2C19 genotypes of the whole blood of all patients were detected by using the method of polymerase chainreaction restriction-fragment length polymorphism(PCR-RFLP). All the patients were treated with Voriconazole at the same time and by the same way.Plasma concentration of Voriconazole was measured by the method of fluo rescence polarization immunoassay.The impact of CYP2C19 genotypes on plasma minimum concentration of voriconazole was analyzed by using the rank sum test. Results Typing results showed that the incidence of iuhomozygous extensive metabolizers (EM) genotype (CYP2C19* 1/*1) was 30%(6/20 cases); the incidence of mixed sub extensive metabolizers (IM) genotype (CYP2C19*1/*2 or CYP2C19*1/*3) was 45%(9/20 cases), among which , CYP2C19*1/*2 was in 4 cases, CYP2C19*1/*3 was in 5 cases; and that of poor metabolizer (PM) genotype (CYP2C19*2/*2 or CYP2C19*2/*3 or CYP2C19*3/*3) was 25%(5/20 cases), among which, CYP2C19*2/*2 was in 3 cases, CYP2C19*2/*3 was in 1 case, and CYP2C19*3/*3 was in 1 case.The serum trough concentration of Voriconazole in EM group, IM group and PM group was(2.30±0.50) mg/L, (3.23±0.71) mg/L, (4.84±0.29) mg/L, respectively.There was a statistically significant relationship between CYP2C19 genotype and plasma minimum concentration of Voriconazole (F=26.99, P=0.032). Conclusions CYP2C19 polymorphism has a significant effect on the minimum concentration of Voriconazole in children with hematological malignancies complicated with invasive fungal infection, which indicates that administration of Voriconazole for clinical treatment should be based on individual CYP2C19 genotype. Key words: Voriconazole; CYP2C19; Gene polymorphism; Plasma drug concentration; Invasive fungal infection