CYP2C19基因多态性联合C-反应蛋白指导伏立康唑在血液病患者并侵袭性真菌感染防治中的应用  

Combined use of CYP2C19 polymorphism analysis and CRP test to guide the use of voriconazole in the prevention and treatment of invasive fungal infections in patients with hematological diseases

作　　者：周丽娟 桑智慧 李慧红 申明慧 郭志强 何勐 秦福丽 ZHOU Li-juan;SANG Zhi-hui;LI Hui-hong;SHEN Ming-hui;GUO Zhi-qiang;HE Meng;QIN Fu-li(Translational Medicine Center,Zhengzhou Central Hospital Affiliated to Zhengzhou University,Zhengzhou 450007,China;Xinxiang Medical University,Xinxiang 453003,China;Department of Hematology,Zhengzhou Central Hospital Affiliated to Zhengzhou University,Zhengzhou 450007,China;Department of Pharmacy,Zhengzhou Central Hospital Affiliated to Zhengzhou University,Zhengzhou 450007,China)

机构地区：[1]郑州大学附属郑州中心医院转化医学中心,郑州450007 [2]新乡医学院,新乡453003 [3]郑州大学附属郑州中心医院血液科,郑州450007 [4]郑州大学附属郑州中心医院药学部,郑州450007

出　　处：《中国新药杂志》2024年第22期2352-2358,共7页Chinese Journal of New Drugs

基　　金：河南省医学科技攻关项目(LHGJ20230777,LHGJ20191056,2018020784);河南省科技攻关计划项目(222102310224);2021年河南省医学教育研究项目(Wjlx2021410)。

摘　　要：目的:探讨CYP2C19基因多态性和C-反应蛋白(C-reactive protein,CRP)联合指导药物治疗监测(therapeutic drug monitoring,TDM)对血液病并侵袭性真菌感染患者伏立康唑(voriconazole,VCZ)用药的指导意义。方法:前瞻性研究选取郑州大学附属郑州中心医院血液科收治的血液病并侵袭性真菌感染接受VCZ治疗的患者139例为研究对象,分为A组(未发生不良反应)和B组(发生不良反应)。采用RT-PCR法检测CYP2C19基因型,RP-HPLC法检测血药谷浓度(C_(min))。比较两组在不同基因表型、CRP分层间C_(min)的差异及疗效差异,Logistic分析CYP2C19基因表型、CRP、C_(min)和VCZ所致不良反应的相关性。结果:A组中UM/RM/PM和IM型患者的比率分别显著低于(P<0.05)或高于B组(P<0.05),其余一般临床资料和疗效在两组间均无显著差异(P均>0.05)。A组VCZ的C_(min)显著低于B组(P=0.009)。VCZ的C_(min)在CYP2C19的各基因表型间无显著差异(P=0.137),PM型患者却显著高于IM型患者(P=0.048),但在CRP不同分层间存在显著差异(P=0.015)。VCZ的C_(min)的增高是导致VCZ发生肝毒性的独立危险因素。结论:CYP2C19基因表型联合CRP水平指导TDM进行VCZ个体化给药,有助于患者获得目标谷浓度,提高疗效和安全性,促进VCZ的精准用药。Objective:To investigate the clinical significance of CYP2C19 polymorphism analysis and C-reactive protein(CRP)test for guiding therapeutic drug monitoring(TDM)of voriconazole(VCZ)in patients with hematologic diseases and invasive fungal infections.Methods:A prospective study was conducted in 139 patients with invasive fungal infections in the Department of Hematology,Zhengzhou Central Hospital affiliated to Zhengzhou University.The patients were divided into group A(without ADRs)and group B(with ADRs).CYP2C19 genotypes were detected by RT-PCR and C_(min)by RP-HPLC.The C_(min)and clinical efficacy in different gene phenotypes and CRP stratification were compared between the two groups.The correlation of CYP2C19 genotype,CRP,C_(min)with VCZ-induced adverse drug reaction was analyzed by Logistic regression.Results:The ratios of UM/RM/PM and IM patients in group A were significantly lower(P<0.05)or higher(P<0.05)than those in group B,respectively.There was no significant difference in other general clinical data and efficacy between the two groups(all P>0.05).The VCZ-C_(min)in group A was significantly lower than that in group B(P=0.009).There was no significant difference in VCZ-C_(min)among the CYP2C19 gene phenotypes(P=0.137).However,the VCZ-C_(min)was significantly higher in PM patients than that in IM patients(P=0.048).A significant difference was observed for VCZ-C_(min)among different levels of CRP(P=0.015).The increase of VCZ-C_(min)was an independent risk factor for VCZ-induced liver toxicity.Conclusion:The combination of CYP2C19 gene phenotype and CRP level may guide TDM for individualized VCZ administration,helping patients to achieve target C_(min),thus improving efficacy and safety.

关 键 词：伏立康唑 CYP2C19 血药谷浓度 疗效 不良反应 

分 类 号：R978.5[医药卫生—药品]