地中海贫血患儿造血干细胞移植术后伏立康唑谷浓度及AUC的影响因素分析  

Influential factors of voriconazole trough concentration and AUC in pediatric patients with thalassemia undergoing hematopoietic stem cell transplantation

作　　者：刘勇军[1] 伍云 凌雅赟[2] 牛露露 黄天敏 陈鑫 罗艺林 刘滔滔[1] LIU Yongjun;WU Yun;LING Yayun;NIU Lulu;HUANG Tianmin;CHEN Xin;LUO Yilin;LIU Taotao(Dept.of Pharmacy,the First Affiliated Hospital of Guangxi Medical University,Nanning 530021,China;Dept.of Pediatrics,the First Affiliated Hospital of Guangxi Medical University,Nanning 530021,China)

机构地区：[1]广西医科大学第一附属医院药学部,南宁530021 [2]广西医科大学第一附属医院儿科,南宁530021

出　　处：《中国药房》2024年第20期2499-2504,共6页China Pharmacy

基　　金：广西自然科学基金项目(No.2021GXNSFAA196037)。

摘　　要：目的分析地中海贫血患儿造血干细胞移植(HSCT)术后伏立康唑(VRZ)谷浓度(c_(min))和药时曲线下面积(AUC)的影响因素。方法选择2021年1月至2024年1月于我院接受HSCT并使用VRZ预防或治疗侵袭性真菌感染的地中海贫血患儿60例,采用高效液相色谱法测定VRZ的血药浓度并计算AUC;采用多元线性回归分析影响VRZ c_(min)、AUC的独立因素。结果共得到60例患儿的120例次VRZ c_(min),26例患儿的27例次VRZ AUC。VRZ c_(min)的中位浓度是0.31 mg/L,其中0.5~5 mg/L有46例次(38.33%),>5 mg/L有2例次(1.67%),<0.5 mg/L有72例次(60.00%);VRZ AUC的中位数是11.68 mg·h/L。患儿体重、HSCT术后时间、淋巴细胞计数以及是否合用苯妥英钠、他克莫司、环孢素对VRZ c_(min)有显著影响(P<0.05);淋巴细胞计数和是否合用苯妥英钠对VRZ AUC有显著影响(P<0.05)。结论患儿体重、HSCT术后时间、淋巴细胞计数以及是否合用苯妥英钠、他克莫司、环孢素是影响VRZ c_(min)的独立因素,淋巴细胞计数、是否合用苯妥英钠是影响VRZ AUC的独立因素。OBJECTIVE To analyze the influential factors on trough concentration(c_(min))and area under the drug concentration time curve(AUC)of voriconazole(VRZ)in pediatric patients with thalassemia undergoing hematopoietic stem cell transplantation(HSCT).METHODS A total of 60 pediatric patients with thalassemia undergoing HSCT who used VRZ for prevention or treatment of invasive fungal infection were collected in our hospital from January 2021 to January 2024.The plasma concentration of VRZ was measured by high-performance liquid chromatography and the AUC was calculated.The factors affecting c_(min) and AUC of VRZ were analyzed using multiple linear regression.RESULTS A total of 120 cases of VRZ c_(min) in 60 pediatric patients was obtained and 27 cases of VRZ AUC in 26 pediatric patients were obtained.The median concentration of VRZ c_(min) was 0.31 mg/L;46 cases had a c_(min) in 0.5-5 mg/L(38.33%),2 cases had a c_(min)>5 mg/L(1.67%),and 72 cases had a c_(min)<0.5 mg/L.The median AUC of VRZ was 11.68 mg·h/L.The patient’s body weight,HSCT postoperative days,lymphocyte count,and combined use of phenytoin sodium,tacrolimus or cyclosporine had significant effects on VRZ c_(min)(P<0.05).Lymphocyte count and combined use of phenytoin sodium had significant effects on VRZ AUC(P<0.05).CONCLUSIONS The body weight,HSCT postoperative days,lymphocyte count,and combined use of phenytoin sodium,tacrolimus or cyclosporine are independent factors affecting VRZ c_(min).Lymphocyte count and combined use of phenytoin sodium are independent factors affecting VRZ AUC.

关 键 词：伏立康唑 地中海贫血 造血干细胞移植 血药浓度 谷浓度 药时曲线下面积 影响因素 

分 类 号：R969.3[医药卫生—药理学] R978.5[医药卫生—药学]