摘要
目的:探讨CYP2C19基因多态性检测对侵袭性真菌感染患者伏立康唑用药的指导作用,为临床个体化用药提供参考。方法:通过前瞻性非随机对照方法,依据患者是否进行CYP2C19基因检测进行分组,A组(未进行基因检测)和B组(基因检测组),B组根据代谢表型分UM组(超快代谢型),EM组(快代谢型),IM组(中间代谢型),PM组(慢代谢型),均采用标准给药剂量,比较各组血药谷浓度(Cmin)、治疗效果和不良反应。采用RT-PCR法检测基因型,RP-HPLC法检测Cmin。常规治疗前、治疗后3 d、7 d和治疗结束进行血常规、C-反应蛋白(CRP)、细菌学情况、肝、肾功能检测。结果:A组和B组一般临床资料、治疗效果和不良反应发生率,均无显著差异(P均>0.05)。EM、IM和PM 3组间Cmin和不良反应均有显著差异(P均<0.05),PM组的Cmin显著高于EM组(P<0.01),PM组的不良反应发生率分别显著高于EM和IM组(P均<0.01)。单因素分析表明CRP和基因型对Cmin有显著影响(P均<0.05)。结论:基于CYP2C19基因型和炎症严重程度进行伏立康唑起始剂量用药,有助于获得目标谷浓度,提高疗效,避免不良反应发生。
OBJECTIVE To explore the role of CYP2 C19 gene polymorphism in guiding the use of voriconazole in patients with invasive fungal infection and provide reference for clinical individualized medication.METHODS Patients were divided into two groups according to whether CYP2 C19 gene detection was performed or not by prospective non-randomized control method:Group A(without gene detection)and group B(with gene detection).According to metabolic phenotypes,Group B was divided into UM group(ultrarapid metabolism),EM group(extensive metabolism),IM group(intermediate metabolism)and PM group(poor metabolism).A standard administration dosage of voriconazole was adopted in all groups.Serum trough concentration(Cmin),clinical effects and adverse reactions were compared among the four groups.The CYP2 C19 genotype was detected by real-time fluorescence quantitative PCR.The Cmin of voriconazole was measured by HPLC.Blood routine,CRP,bacteriology,liver function and renal function were detected before treatment,at 3 d,7 d after treatment and end of treatment,respectively.RESULTS There was no significant difference between group A and group B in general clinical data,treatment effect and incidence of adverse reactions(all P>0.05).There was significant difference for Cmin and adverse reactions among the three groups(all P<0.05).The average Cmin was higher in group PM than that in group EM(P<0.01).The incidence of adverse reactions was significantly higher in group PM than group EM and group IM(all P<0.01).Univariate analysis indicated a significant effect of CRP and genotype on Cmin(all P<0.05).CONCLUSION Initial dosage of voriconazole based on CYP2 C19 genotype and severity of inflammation may help to obtain target trough concentration,improve clinical effect and avoid adverse reactions.
作者
李敏
周丽娟
张华
郭志强
秦福丽
高延秋
LI Min;ZHOU Li-juan;ZHANG Hua;GUO Zhi-qiang;QIN Fu-li;GAO Yan-qiu(Department of Pharmacy,Zhengzhou Central Hospital Affiliated to Zhengzhou University,Henan Zhengzhou 450007,China;Translational medicine center,Zhengzhou Central Hospital Affiliated to Zhengzhou University,Henan Zhengzhou 450007,China;Respiratory Intensive Care Unit,Zhengzhou Central Hospital Affiliated to Zhengzhou University,Henan Zhengzhou 450007,China;Department of Hematology,Zhengzhou Central Hospital Affiliated to Zhengzhou University,Henan Zhengzhou 450007,China)
出处
《中国医院药学杂志》
CAS
北大核心
2020年第2期156-160,207,共6页
Chinese Journal of Hospital Pharmacy
基金
河南省医学科技攻关计划项目(编号:201602333).
关键词
伏立康唑
CYP2C19
Cmin
疗效
不良反应
voriconazole
CYP2C19
serum tough concentration
clinical effect
adverse reaction
