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·药物与临床·


          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
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          刘勇军 ,伍 云 ,凌雅赟 ,牛露露 ,黄天敏 ,陈 鑫 ,罗艺林 ,刘滔滔 (1.广西医科大学第一附属医院药学
                                                                   1
          部,南宁 530021;2.广西医科大学第一附属医院儿科,南宁 530021)
          中图分类号  R969.3;R978.5      文献标志码  A      文章编号  1001-0408(2024)20-2499-06
          DOI  10.6039/j.issn.1001-0408.2024.20.10
          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(cmin )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 cmin、AUC的独立因素。结果  共得到60
          例患儿的 120 例次 VRZ cmin,26 例患儿的 27 例次 VRZ AUC。VRZ cmin 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 cmin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 cmin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。
          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

          Influential  factors  of  voriconazole  trough  concentration  and  AUC  in  pediatric  patients  with  thalassemia
          undergoing hematopoietic stem cell transplantation
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          LIU Yongjun ,WU Yun ,LING Yayun ,NIU Lulu ,HUANG Tianmin ,CHEN Xin ,LUO Yilin ,LIU Taotao         1
                                                       1
                                                                         1
                     1
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         (1.  Dept.  of  Pharmacy,  the  First Affiliated  Hospital  of  Guangxi  Medical  University,  Nanning  530021,  China;
          2. Dept. of Pediatrics, the First Affiliated Hospital of Guangxi Medical University, Nanning 530021, China)
          ABSTRACT   OBJECTIVE To analyze the influential factors on trough concentration (cmin ) 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 cmin and AUC
          of  VRZ  were  analyzed  using  multiple  linear  regression.  RESULTS  A  total  of  120  cases  of  VRZ  cmin  in  60  pediatric  patients  was
          obtained and 27 cases of VRZ AUC in 26 pediatric patients were obtained. The median concentration of VRZ cmin was 0.31 mg/L;
          46 cases had a cmin in 0.5-5 mg/L(38.33%), 2 cases had a cmin>5 mg/L(1.67%), and 72 cases had a cmin<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  cmin (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
          cmin. Lymphocyte count and combined use of phenytoin sodium are independent factors affecting VRZ AUC.
          KEYWORDS    voriconazole;  thalassemia;  hematopoietic  stem  cell  transplantation;  plasma  concentration;  trough  concentration;
          area under the drug concentration-time curve; influential factors


              地中海贫血是由α或β珠蛋白链基因缺失或突变导                         病。我国约有 3 000 万地中海贫血基因携带者,其中 30
          致的珠蛋白链合成受阻而引起的一种遗传性单基因疾                            万患者为重型地中海贫血或中间型地中海贫血,而造血
                                                             干 细 胞 移 植(hematopoietic  stem  cell  transplantation,
             Δ 基金项目 广西自然科学基金项目(No.2021GXNSFAA196037)
                                                             HSCT)术是目前临床治疗重型地中海贫血最有效、最成
             *第一作者 药师,硕士研究生。研究方向:临床药学。E-mail:
                                                                         [1]
                                                             熟的方法之一 。然而,HSCT术前和HSCT期间化疗药
          1539649553@qq.com
             # 通信作者 主任药师,教授,博士生导师,博士。研究方向:临床                 物和免疫抑制剂的长期使用可能会导致患者出现中性
          药学、抗感染药物治疗、个体化给药。E-mail:liutaotao@gxmu.edu.cn      粒细胞减少和移植物抗宿主病,这些因素可增加侵袭性

          中国药房  2024年第35卷第20期                                              China Pharmacy  2024 Vol. 35  No. 20    · 2499 ·
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