结缔组织病继发血小板减少患者中环孢素A血药浓度监测与评价  

Monitoring and evaluation of blood concentrations of cyclosporine A in patients with secondary thrombocytopenia to connective tissue disease

作　　者：章静欣 赵明明[1] 肇丽梅[1] ZHANG Jing-xin;ZHAO Ming-ming;ZHAO Li-mei(Department of Pharmacy,Shengjing Hospital of China Medical University,Liaoning Shenyang 110004,China)

机构地区：[1]中国医科大学附属盛京医院药学部,辽宁沈阳110004

出　　处：《中国医院药学杂志》2022年第21期2258-2263,共6页Chinese Journal of Hospital Pharmacy

基　　金：国家自然科学基金项目资助(编号:82073936);盛京自由研究者基金(编号:M0779);国家自然科学基金项目资助(编号:81703628)。

摘　　要：目的:探究结缔组织病继发血小板减少(immune thrombocytopenia secondary to connective tissue disease,CTD-ITP)患者环孢素A血药浓度与疗效相关性,获得环孢素A在该人群治疗的有效浓度下限,为临床用药的有效性和安全性提供参考。方法:回顾性收集中国医科大学附属盛京医院2016年1月至2021年3月间应用环孢素A治疗的CTD-ITP患者的临床及实验室检查数据,分析Css分布与给药剂量、实验室检查结果、基础疾病的关系,受试者工作特征曲线(ROC)确定环孢素A有效浓度下限。结果:共纳入符合标准的患者79例,收集187例次Css监测数据(9~261.5μg·L^(-1))。环孢素A给药剂量与Css存在相关性;随着Css的升高,补体C3和尿素水平呈上升趋势;Css和日剂量分别在不同基础疾病组间存在差异(P<0.05),血小板计数在组间显现差异(P<0.05)。对68例患者的110例次血药浓度监测数据进行有效浓度分析,二元Logistics回归分析结果表明,Css和日给药剂量对疗效有显著性影响(P<0.01)。Css对于疗效的预判准确性优于给药剂量,ROC曲线下面积AUC为0.849 vs.0.738。此时对应的截点为51.95μg·L^(-1),提示当Css大于51.95μg·L^(-1)时,临床治疗有效的概率较高。结论:本研究通过分析环孢素A稳态血药浓度与疗效的相关性,运用ROC曲线分析初步确定了CTD-ITP患者CsA治疗有效浓度下限为51.95μg·L^(-1)。OBJECTIVE To explore the distribution of cyclosporine A serum concentrations in patients with thrombocytopenia secondary to connective tissue disease,and obtain the effective concentration of cyclosporine A in this population,so as to provide reference for the effectiveness and safety of clinical medication.METHODS Clinical and laboratory test data of patients with secondary thrombocytopenia to connective tissue disease treated with cyclosporin A of Shengjing hospital between January 2016 and March 2021 were retrospectively collected.This study analysed the relationship between the distribution of Css and the dosage,lab test results,and basic diseases and effective concentration threshold of cyclosporin A was determined by using the ROC curve.RESULTS A total of 79 patients met the criteria,and a total of 187 blood concentration data were collected(9 to 261.5μg·L^(-1))for the drug concentration distribution study.Blood concentrations and daily dose varied between different underlying CTD groups,and the corresponding platelet counts varied between different groups.The effective concentration study included 110 times of blood drug concentration monitoring of 68 patients who had been using cyclosporine A more than3 months.According to the clinical manifestations and laboratory tests,the patients were divided into effective group(68 cases)and ineffective group(42 cases).Binary logistic regression analysis showed that the blood concentration and daily dose of cyclosporine A had significant effects on the curative effect(P<0.0001).The prediction accuracy of blood concentration for efficacy is better than that of dosage,where the area under the ROC curve AUC0.849 vs.0.739.The corresponding cut-off point of the optimal critical value is 51.95μg·L^(-1),indicating that when Css is greater than 51.95μg·L^(-1),the probability of effective clinical treatment is higher.CONCLUSION This study analyzed the correlation between the steady-state blood concentration of cyclosporine A and the efficacy,the threshold of cyclosporin

关 键 词：结缔组织病 环孢素A 血小板减少 血药浓度 

分 类 号：R969[医药卫生—药理学]