基于CYP2C19基因多态性检测指导伏立康唑治疗肺结核合并肺曲霉病的疗效及影响因素分析  

Efficacy of voriconazole in the treatment of pulmonary tuberculosis complicated with chronic pulmonary aspergillosis based on CYP2C19 gene polymorphism detection and the factors affecting the efficacy

作　　者：陈永刚 喻明丽 罗季 张文林 和进堂 肖琦琦 王俊龙 彭江丽 CHEN Yonggang;YU Mingli;LUO Ji;ZHANG Wenlin;HE Jintang;XIAO Qiqi;WANG Junlong;PENG Jiangli(Department of Pharmacy,the Third People’s Hospital of Kunming,Kunming 650041,China)

机构地区：[1]昆明市第三人民医院药学部,昆明650041 [2]大理大学药学院 [3]昆明市第三人民医院结核科,昆明650041

出　　处：《中国感染与化疗杂志》2025年第2期132-139,共8页Chinese Journal of Infection and Chemotherapy

基　　金：昆明市卫健委科研基金(2023-13-01-025,2023-13-01-004)。

摘　　要：目的 探讨肺结核合并肺曲霉病(CPA)患者在CYP2C19基因多态性检测下应用伏立康唑抗曲霉的治疗效果及疗效影响因素,为临床提供靶向治疗指导。方法 将2018年12月-2022年11月昆明市第三人民医院结核科收治的207例肺结核并发CPA患者按照随机数字表法分为观察组105例和对照组102例,对照组采用常规伏立康唑治疗方案,观察组根据CYP2C19基因型检测结果制定伏立康唑给药方案,分析两组以及基于不同CYP2C19基因型分组间的血药浓度情况,评估疗效及安全性,并以疗效为因变量,采用logistic回归方法分析疗效的影响因素。结果 观察组伏立康唑血药浓度及抗曲霉总有效率均显著优于对照组(P<0.05)。观察组患者CYP2C19基因位点分析检出快代谢型(EM) 37例,中间代谢型(IM)47例,慢代谢型(PM) 21例。EM、IM的伏立康唑血药浓度差异无统计学意义(P>0.05),两者均低于PM,差异有统计学意义(P<0.05);PM临床总有效率为100%,IM组为91.5%,EM组为83.8%,差异有统计学意义(P<0.05),对比三种基因型组间不良反应发生率差异无统计学意义(P>0.05)。多因素logistic回归分析结果显示,肺部空洞、低蛋白血症、粒细胞缺乏均与疗效显著相关(P<0.05)。结论 根据CYP2C19基因多态性,对肺结核合并CPA患者个体化应用伏立康唑抗曲霉治疗,可有效改善症状,提升临床疗效,具有重要的临床价值,同时需警惕低蛋白血症、粒细胞缺乏、肺部空洞等危险因素对肺曲霉病疗效的影响。Objective To investigate the efficacy of voriconazole in the treatment of pulmonary tuberculosis complicated with chronic pulmonary aspergillosis(CPA)based on CYP2C19 gene polymorphism detection and examine the factors affecting the efficacy for improving targeted therapy in clinical practice.Methods A total of 207 patients with pulmonary tuberculosis complicated with CPA treated in the Third People’s Hospital of Kunming from December 2018 to November 2022 were randomly assigned to an observation group(105 cases)or a control group(102 cases).The patients in the control group received standard voriconazole treatment,while the patients in the observation group had their voriconazole regimen tailored based on CYP2C19 genotyping results.Plasma drug concentration levels,efficacy,and safety were compared between the two groups and in terms of CYP2C19 genotypes.Logistic regression analysis was used to identify the factors affecting treatment efficacy.Results The observation group showed significantly higher plasma voriconazole concentrations and overall antifungal efficacy compared to the control group(P<0.05).In the observation group,CYP2C19 genotyping identified 37 extensive metabolizers(EM),47 intermediate metabolizers(IM),and 21 poor metabolizers(PM).Plasma concentration of voriconazole did not show significant difference between EM and IM(P>0.05),but both PM and IM were associated with significantly lower plasma concentration of voriconazole than PM(P<0.05).The clinical efficacy rate was 100%for PM,91.5%for IM,and 83.8%for EM(P<0.05).The incidence of adverse events did not show significant difference among the three genotypes(P>0.05).Logistic regression analysis revealed that lung cavitation,hypoalbuminemia,and agranulosis were significantly correlated with therapeutic efficacy(P<0.05).Conclusions CYP2C19 gene polymorphism detection is valuable in clinical practice.It can inform anti-aspergillus therapy with voriconazole to effectively improve symptoms and clinical efficacy in patients with pulmonary tuberculosis

关 键 词：CYP2C19基因多态性 肺结核 肺曲霉病 伏立康唑 疗效 影响因素 

分 类 号：R978.5[医药卫生—药品] R521[医药卫生—药学] R519.8