Effect of CYP2C19 polymorphism on Voriconazole Cmin in children with hematological malignancies compli-cated with invasive fungal infection / 中华实用儿科临床杂志

ABSTRACT

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 chain-reaction 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 me-tabolizers (EM)genotype (CYP2C19* 1 /*1 )was 30%(6 /20 cases);the incidence of mixed sub extensive metaboli-zers (IM)genotype (CYP2C19*1 /*2 or CYP2C19*1 /*3)was 45%(9/20 cases),among which ,CYP2C19*1 /*2 was in 4 cases,CYP2C1 9*1 /*3 was in 5 cases;and that of poor metabolizer (PM)genotype (CYP2C1 9*2 /*2 or CYP2C1 9*2 /*3 or CYP2C1 9*3 /*3)was 25%(5 /20 cases),among which,CYP2C1 9*2 /*2 was in 3 cases, CYP2C1 9*2 /*3 was in 1 case,and CYP2C1 9*3 /*3 was in 1 case.The serum trough concentration of Voriconazole in EMgroup,IMgroup and PMgroup was(2.30 ±0.50)mg/L,(3.23 ±0.71 )mg/L,(4.84 ±0.29)mg/L,respec-tively.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 mini-mum concentration of Voriconazole in children with hematological malignancies complicated with invasive fungal infec-tion,which indicates that administration of Voriconazole for clinical treatment should be based on individual CYP2C19 genotype.