【作者】 王刚； 肖剑文； 戴碧涛； 何翠瑶； 袁拥华； 刘彬；

【Author】 WANG Gang;XIAO Jian-wen;DAI Bi-tao;HE Cui-yao;YUAN Yong-hua;LIU Bin;Department of Clinial Pharmacy, Children’s Hospital of Chongqing Medical University;

【机构】 重庆医科大学附属儿童医院临床药学研究室； 重庆医科大学附属儿童医院血液病房；

【摘要】 目的:建立环孢素A在再生障碍性贫血（AA）患儿中群体药代动力学（PPK）模型,获取个体药动学（PK）参数,结合WBC、Hb、PLT等效应指标,优化治疗方案。方法:收集诊断为AA的69例住院、门诊患儿的相关临床资料,以NONMEM程序建立并验证CsA的PPK模型,根据PK参数制定最优化的治疗方案,结合疗效指标分析CsA血药浓度与疗效的关系。结果:CsA基础PK模型为线性二房室模型,PK参数个体间变异为指数模型,个体内变异为加法模型,总模组群体峰浓度（C₂）为（490.79±196.22） ng·mL^-1,谷浓度（C₀）为（129.81±59.21）ng·mL^-1;CsA血药浓度与治疗效应指标WBC、Hb、PLT之间存在较强正相关（R²>0.5）,有效率与谷浓度（C₀）的相关性（R²=0.434）明显优于峰浓度（C₂）的相关性（R²=0.198）,有效率的95%置信分析谷浓度变异较峰浓度小。结论:谷浓度（C₀）为检测实施个体化治疗更有价值的临床参考。更多还原

【Abstract】 OBJECTIVE To establish the population pharmacokinetics（PPK） model of cyclosporin A in children aplastic anemia（AA） and to obtain individual parameters. Considering therapeutic indexes such as WBC、Hb、PLT,we can optimize the regimen. METHODS The related clinical data of 69 children aplastic anemia in our hospital was collected to establish and validate the population pharmaco-kinetics of cyclosporin A by NONMEM method.According to the individual parameters,we can frame the best treatment strategy, and refer to therapeutic indexes then analyse the correlation between cyclosporin A concentration in blood and efficacy.Results:The elementary individual parameters of cyclosporin A was a linear two compartment model with exponential interindividual variability and additive residual error statistical model.The total population peak concentration（C₂） were（490.79±196.22） ng·mL^-1,the valley concentration（C₀） were（129.81±59.21） ng·mL^-1;there were strong positive correlations（R²>0.5） between cyclosporin A concentration in blood and indexes like WBC、Hb、PLT,the correlation（R² = 0.434）between effective rate and valley concentration was obviously higher than that（R² = 0.198） between effective rate and peak concentration.Comparing with the peak concentration,the valley concentration’s changes of efficiency’s 95% confidence interval analysis were smaller. CONCLUSIONS As the reference of checking and performing individual treatment,the valley concentration was more suitable.更多还原