有限取样法估算霉酚酸在自身免疫性疾病患者的体内暴露药量

发布时间：2018-03-06 01:15

本文选题：有限取样法　切入点：霉酚酸　出处：《中国药学杂志》2015年23期 　论文类型：期刊论文

【摘要】：目的建立有限取样法估算霉酚酸(MPA)在自身免疫性疾病(AID)患者的体内暴露药量(AUC)。方法24例AID患者服用霉酚酸醋(MMF)0.75 g,q12 h,达稳态后,检测服药前即刻、服药后0.5,1,1.5,2,4,6,8和12h活性代谢物MPA的血药浓度梯形法计算各例实测AUC_(0-12 h);将24例患者数据资料随机平分为模型资料组与验证资料组,对模型资料组的数据采用多元线性回归法分别拟合1~4个采血点估算AUC_(0-12 h)的数学模型对初选模型用验证资料组数据检验预测偏差和精密度,并结合临床实际情况选择最佳模型。结果 12h谷浓度建立的单点预测模型r~2值为0.957平均预测误差及绝对预测误差分别为-3.93与11.93,均15%;0.5,1.5,6,8 h或1.5,6,8,12h四点拟合的模型与AUC_(0-12 h)的相关性均达0.996,验证后预测误差在±15%以内的例数为9例;另有2点模型与3点模型,预测效果介于上述两种模型之间。结论结合临床实际情况,精确度较高的四点模型AUC=3.19+0.49c_(0.5h)、+1.76c_(1.5h)+2.95c_(6h)+5.46c_(8h)适用于晨起服药后取血监测的住院患者;相对简便的单点模型AUC=10.82+13.37c_(12 h)适用于夜间服药次日晨起入院监测的门诊患者。Bland-Altman分析显示,两种模型均能较好预测使用MMF+甲泼尼龙二联免疫抑制方案的中国成年AID患者的MPA AUC。
[Abstract]:Objective to establish a limited sampling method to estimate the exposure of mycophenolate mofetil (MPA) in vivo to patients with autoimmune disease (AIDD). Methods 24 patients with AID were treated with MMFX 0.75 g / q12 h. The serum concentration of active metabolite MPA was calculated by trapezoid method after taking the drug, and 24 patients were randomly divided into model data group and validation data group, and 24 patients were randomly divided into model data group and validation data group, and 24 patients were randomly divided into model data group and validation data group, and 24 patients were randomly divided into model data group and validation data group, and 24 patients were randomly divided into two groups. Multiple linear regression method was used to fit 1 ~ 4 blood sampling points to estimate AUC_(0-12 h in the model group. The prediction deviation and precision of the primary model were tested with the data of the validation data group. Results the average prediction error and absolute prediction error of single point prediction model established by 12h valley concentration were -3.93 and 11.93, respectively. The correlation was 0.996, and the number of cases whose prediction error was less than 卤15% after verification was 9 cases. There were two and three models, the prediction effect was between the above two models. Conclusion the four-point model AUC=3.19 0.49cStamp 0.5hm, 1.76cStamp 1.5h) 2.95cSta6h) is suitable for the in-patients who take blood for monitoring after taking medicine in the morning. Bland-Altman analysis showed that the two models could be used to predict the MPA of Chinese adult AID patients using MMF methylprednisolone immunosuppressive regimen.
【作者单位】：同济大学附属杨浦医院临床药学与药理学研究室;同济大学附属杨浦医院肾内科;
【基金】：国家自然科学基金青年项目资助项目(81302741) 上海市杨浦区“百医登高”计划资助项目
【分类号】：R969.4

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