儿童应用西罗莫司血药浓度波动2例原因分析  

Analysis of the fluctuation of blood concentration in children using sirolimus:A case report

作　　者：徐晓琳 韩彤昕[2] 成晓玲[1] 王晓玲[1] 毛华伟 XU Xiaolin;HAN Tongxin;CHENG Xiaoling;WANG Xiaoling;MAO Huawei(Department of Pharmacy,Beijing Children's Hospital,Capital Medical University,National Center for Children's Health,Beijing 100045,China;Department of Immunity,Beijing Children's Hospital,Capital Medical University,National Center for Children's Health,Beijing 100045,China)

机构地区：[1]国家儿童医学中心,首都医科大学附属北京儿童医院药学部,北京100145 [2]国家儿童医学中心,首都医科大学附属北京儿童医院免疫科,北京100145

出　　处：《中国循证儿科杂志》2022年第3期235-239,共5页Chinese Journal of Evidence Based Pediatrics

基　　金：重大新药创制科技重大专项:2017ZX09304029;北京市自然科学基金委,北京市自然科学基金-海淀原始创新联合基金:L212013;首都卫生发展科研专项项目:首发2022-2Z-2099。

摘　　要：背景西罗莫司(SRL)在患儿中的应用涉及器官移植、自身免疫病、淋巴管畸形、血管畸形、结节性硬化症等疾病,但SRL具有较大的药代动力学变异性,需进行药物监测。目的提出解决SRL血清药物浓度变化的方案及其原因。设计病例报告。方法描述2例免疫缺陷病患儿应用SRL治疗6个月的临床资料,分析患儿出现药物浓度异常值的原因,并行文献复习。主要结局指标SRL全血谷浓度(Cmin)达到目标范围5~10 ng·mL^(-1)。结果例1,SRL与伏立康唑的药物相互作用、CYP3A5 rs776746C/C基因型是导致药物代谢变慢和血药浓度升高的原因,剂量降至初始剂量的20%,SRL血药浓度逐渐恢复至达标范围。例2,CYP3A5基因rs776746C/C型和ABCB1基因rs1045642 T/T型是药物清除率减低和Cmin异常升高的原因,给药剂量降至初始剂量的50%后,SRL血药浓度逐渐下降至正常,治疗浓度一直在达标范围内。结论在调整治疗方案前考虑确定SRL的Cmin异常值原因的样本、临床和遗传因素应加以考虑,优化患儿的SRL综合治疗管理。Background Sirolimus(SRL)is used in children for organ transplantation,autoimmune diseases,lymphatic malformation,vascular malformation,tuberous sclerosis and other diseases.However,it has great pharmacokinetic variability,which requires therapeutic drug monitoring(TDM).Objective To reveal the causes of abnormal serum concentration of sirolimus.Design Case report.Methods We described the clinical data of 2 children with immunodeficiency treated with SRL for 6 months,analyzed the causes of abnormal drug concentration in children,and reviewed the literature.Main outcome measures Whole blood trough concentration(Cmin)reached the target range of 5-10 ng·mL^(-1).Results For child A,the drug interaction between SRL and voriconazole and CYP3A5 rs776746C/C genotype were the reasons for the slow drug metabolism and abnormal increase of Cmin.The dose decreased to 20%of the initial dose and gradually returned to the standard range.For child B,CYP3A5 rs776746 C/C genotype and ABCB1 gene rs1045642 T/T genotype were the reasons for the decrease of drug clearance rate and the abnormal increase of Cmin.After reducing the initial dose to 50%,the serum concentration of SRL gradually decreased to normal,and the treatment concentration was within the standard range.Conclusion Systematic method will help to determine the cause of Cmin abnormal value of SRL.The sample factors,clinical factors and genetic factors should be considered before adjusting the treatment plan,and the comprehensive treatment management(CMM)of SRL should be optimized.

关 键 词：西罗莫司 CYP3A5 ABCB1 药物基因组 治疗药物监测 

分 类 号：R969.1[医药卫生—药理学]