UGT1A4^(*)3基因多态性对恶性血液病患者泊沙康唑血药浓度及侵袭性真菌病预防疗效的影响  

Effect of UGT1A4^(*)3 gene polymorphism on posaconazole plasma concentration and preventive efficacy of invasive fungal disease in hematological malignancy patients

作　　者：张飞雨 张瑞霞[2] 魏晓晨[2] 赵佳[3] 张弋[2] 朱明辉 ZHANG Feiyu;ZHANG Ruixia;WEI Xiaochen;ZHAO Jia;Zhang Yi;ZHU Minghui(Department of Pharmacy,Tianjin Third Central Hospital,Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases,Artificial Cell Engineering Technology Research Center,Tianjin Institute of Hepatobiliary Disease,Tianjin 300170,China;Department of Pharmacy,Tianjin First Central Hospital,Tianjin 300192,China;Department of Pharmacy,Tianjin Chest Hospital,Tianjin 300192,China)

机构地区：[1]天津市第三中心医院药学部,天津市重症疾病体外生命支持重点实验室,天津市人工细胞工程技术研究中心,天津市肝胆疾病研究所,天津300170 [2]天津市第一中心医院药学部,天津300192 [3]天津市胸科医院药学部,天津300222

出　　处：《中国医院药学杂志》2024年第22期2628-2632,共5页Chinese Journal of Hospital Pharmacy

基　　金：天津药学中青年科研项目(编号:TJYX2023-01);天津市教委科研项目(编号:2023YXZX02)。

摘　　要：目的:分析恶性血液病患者UGT1A4^(*)3基因多态性对泊沙康唑血药浓度及侵袭性真菌病预防疗效的影响,探讨泊沙康唑血药浓度不达标的危险因素,为临床个体化用药提供参考。方法:收集2020年10月至2022年6月服用泊沙康唑的恶性血液病患者临床资料,测定患者泊沙康唑血药浓度及其UGT1A4基因型,记录患者侵袭性真菌病预防疗效并分析基因型对其影响,探讨基因多态性、年龄、性别、体质量指数(BMI)、肝肾功能等因素对泊沙康唑血药浓度的影响。结果:共纳入121例患者,监测泊沙康唑血药浓度279例次。携带UGT1A4^(*)3突变基因患者的泊沙康唑血药浓度显著低于野生型(P=0.009),但基因多态性对最终侵袭性真菌病的预防疗效并无显著影响(P>0.05)。UGT1A4^(*)3基因多态性、性别、BMI、腹泻呕吐为泊沙康唑血药浓度不达标的独立危险因素(P<0.05)。结论:影响泊沙康唑血药浓度不达标的危险因素较多,用药过程建议密切监测,临床应结合患者UGT1A4^(*)3基因型、性别、BMI、是否合并腹泻呕吐等因素及时调整泊沙康唑的给药剂量或剂型,以保障用药的安全性和有效性。OBJECTIVE To explore the effect of UGT1A4^(*)3 gene polymorphism on plasma concentration of posaconazole(PCZ)and preventive efficacy of invasive fungal disease in patients with malignant hematological diseases and explore the risk fac-tors for substandard plasma concentration of PCZ to provide references for clinical individualized medication.METHODS From October 2020 to June 2022,the relevant clinical data were retrospectively reviewed for 121 hematological patients on a therapy of PCZ.Plasma concentration of PCZ and UGT1A4 genotype were determined.The efficacy of invasive fungal disease prophylaxis was recorded and the influence of genotype analyzed.The effects of gene polymorphism,age,gender,body mass index(BMI),hepaticorenal function and other factors on PCZ plasma concentration were examined.RESULTS Plasma concentration was PCZ of monitored 279 times.Cmin of PCZ in individuals with UGT1A4^(*)3 mutation was significantly lower than that in those with wild type(P=0.009).However,gene polymorphism had no significant effect on final prophylactic efficacy of invasive fungal disease(P>0.05).UGT1A4^(*)3 gene polymorphism,gender,BMI,diarrhea and vomiting were independent risk factors for substandard blood concentration of PCZ(P<0.05).CONCLUSION There are many risk factors affecting blood concentration of PCZ.It is prudent to closely monitor the medication process.The dose or dosage form of PCZ should be adjusted in time according to indi-vidual profiles of UGT1A4^(*)3 genotype,gender,BMI and whether or not complicated with diarrhea and vomiting to ensure the safetv and effectiveness of medication.

关 键 词：泊沙康唑 UGT1A4^(*)3 基因多态性 治疗药物监测 

分 类 号：R969[医药卫生—药理学]