Study On The Relationship Between CYP2C19 Gene Polymorphism And The Pharmacokinetics And Adverse Reactions Of Voriconazole In Patients With Hematological Diseases

Objective:To investigate the relationship among CYP2C19 gene polymorphisms and plasma concentrations of voriconazole and adverse drug reactions in patients with hematopathy by CYP2C19 gene detection and concentration monitor of voriconazole.Methods:Blood samples from 96 patients with hematological diseases were collected and the drug concentration of voriconazole was detected dynamically.Gene detection was performed on two sites of rs4244285 and rs498689.Statistical analysis was used to compare the plasma concentration of voriconazole among different genotypes and the difference between the incidence of adverse reactions.Results:(1)The plasma trough concentrations of patients with poorly metabolized(PMs)were significantly higher than those of normal(Homs)and intermediate metabolites(Hems).(2)The incidence of adverse reactions was higher in patients with poorly metabolites(PM)and intermediate metabolites(Hem)than with normal metabolites(Em),but no statistical difference was found in the incidence of adverse reactions between any two metabolitesConclusion:There is a close relationship between CYP2C19 gene polymorphism and voriconazole plasma concentration.Although,there is no statistical difference between the incidence of adverse with different genotypes in this study,the incidence of adverse reactions in PMS and HEMs significantly higher than Ems should be taken into attention.The relationship between genotype safety and efficacy will become more and more clearer with more extensive and in-depth research of CYP2C19 genetic polymorphisms,which will provide a better individualized treatment for patientsObjective:To explore the correlation between trough concentration and adverse reactions by dynamically monitoring the plasma concentration of voriconazole in patients with hematologic diseases,and to investigate the interventions when adverse reactions occurred in some cases.Methods:The plasma trough concentrations of voriconazole in patients with hematologic diseases was monitored and the incidence of adverse drug reactions was observed.The correlation between drug concentration and clinical response was analyzed.The maintenance doses were adjusted if adverse reactions occured.Results:(1)After treatment,the rate of adverse reactions in patients with concentrations ranging from 1.0 to 5.0 ?g·mL-1 and concentrations>5.0?g·mL-1 is 11%and 41%respectively(P=0.0006).(2).The trough concentration of patients with adverse reactions is higher than the ones without adverse reactions(P=0.0236).(3)In patients with adverse reactions,9 patients were treated with dose reduction.After doses reduction,adverse reactions only remained in 1 patient,and disappeared or decreased in 8 patients(all cured at last).Conclusion:Voriconazole plasma concentration varies widely among individuals and the level of drug concentration is closely related to adverse reactions.Clinical drug adjustment according to dynamic monitoring of voriconazole plasma concentration of patients will help improve efficacy and safety.