摘要
目的探讨系统性红斑狼疮(SLE)患者口服西罗莫司稳态血药浓度的影响因素。方法回顾性纳入2019年7月至2023年4月接受西罗莫司治疗的SLE患者,收集患者人口学资料、合并用药及实验室指标。按稳态血药浓度/剂量(C_(0)/D)四分位分组,采用非参数检验、Spearman相关及多元线性回归进行统计分析。结果共纳入228例次血药浓度监测数据。女性患者占比90%。按性别及年龄分组,不同性别、不同年龄比较C_(0)/D均无显著差异(P>0.05),老年组西罗莫司日剂量显著低于青年组(P<0.05)。西罗莫司日剂量与血药浓度结果呈显著弱相关性(r=0.256,P<0.01);按C_(0)/D分组,高C_(0)/D组白蛋白(ALB)降低,总胆红素(TBIL)、天冬氨酸转氨酶(AST)、丙氨酸转氨酶(ALT)、γ-谷氨酰转移酶(γ-GT)、血清补体C3及尿微量白蛋白/肌酐(ACR)升高(P<0.05)。多元回归显示ALB、AST、ALT、C3和ACR是C_(0)/D的独立影响因素(P<0.05)。结论西罗莫司血药浓度在SLE患者中表现出显著的个体差异,受肝功能及补体C3显著影响,而与性别、年龄无关。建议临床定期监测血药浓度及肝肾功能、免疫学指标,以实现个体化给药。
AIM To explore the factors influencing steady-state blood concentration of oral sirolimus in patients with systemic lupus erythematosus(SLE).METHODS A retrospective analysis was conducted on SLE patients treated with sirolimus between July 2019 and April 2023.Demographic data,concomitant medications,and laboratory indicators were collected.Patients were grouped based on quartiles of steady-state blood concentration/dose(C_(0)/D).Statistical analyses included non-parametric tests,Spearman correlation,and multiple linear regression.RESULTS A total of 228 therapeutic drug monitoring data points were included.Female patients accounted for 90%of the cohort.When grouped by gender and age,no significant differences in C_(0)/D were observed between groups(P>0.05).However,the daily dose of sirolimus in the elderly group was significantly lower than that in the younger group(P<0.05).A weak but significant correlation was found between the daily dose of sirolimus and blood concentration(r=0.256,P<0.01).When grouped by C_(0)/D,the high C_(0)/D group exhibited decreased albumin(ALB)levels and elevated total bilirubin(TBIL),aspartate aminotransferase(AST),alanine aminotransferase(ALT),γ-glutamyl transferase(γ-GT),C3,and urine microalbumin/creatinine ratio(ACR)(P<0.05).Multiple regression analysis identified ALB,AST,ALT,C3,and ACR as independent influencing factors of C_(0)/D(P<0.05).CONCLUSION The blood concentration of sirolimus exhibits significant interindividual variability in SLE patients.This variability of is notably influenced by liver function and complement C3 levels but is unrelated to gender or age.Regular monitoring of blood concentration,liver and kidney function,and immunological indicators is recommended to achieve personalized dosing.
作者
傅毓
熊寒斌
汪保林
杜文鹏
张秀灵
余乐
段新旺
熊爱珍
何佳珂
FU Yu;XIONG Han-bin;WANG Bao-lin;DU Wen-peng;ZHANG Xiu-ling;YU Le;DUAN Xin-wang;XIONG Ai-zhen;HE Jia-ke(Department of Pharmacy,the Second Affiliated Hospital of Nanchang University,Nanchang JIANGXI 330006,China;Department of Rheumatology and Immunology,the Second Affiliated Hospital of Nanchang University,Nanchang JIANGXI 330006,China;Department of Pharmacy,Nanchang County Peoples Hospital,Nanchang JIANGXI 330200,China)
出处
《中国新药与临床杂志》
北大核心
2025年第10期757-762,共6页
Chinese Journal of New Drugs and Clinical Remedies
基金
国家自然科学基金(82160707,82060677)
江西省自然科学基金青年重点项目(20202ACB216005)
江西省主要学科学术和技术带头人培养计划-青年人才项目(20204BCJL23053)。
关键词
系统性红斑狼疮
西罗莫司
治疗药物监测
systemic lupus erythematosus
sirolimus
therapeutic drug monitoring
