针对在实验室中观测污泥絮凝-沉降过程及污泥颗粒絮团粒径分布情况存在盲点的问题,运用群平衡体模型(PBM)定义污泥颗粒的的尺寸,通过Lou模型与Ghadiri模型分别模拟污泥颗粒间的聚合及破碎机理,耦合PBM及两相流混合模型对Jeriffa De Cle...针对在实验室中观测污泥絮凝-沉降过程及污泥颗粒絮团粒径分布情况存在盲点的问题,运用群平衡体模型(PBM)定义污泥颗粒的的尺寸,通过Lou模型与Ghadiri模型分别模拟污泥颗粒间的聚合及破碎机理,耦合PBM及两相流混合模型对Jeriffa De Clercp等在沉降桶内的污泥沉降实验进行三维数值模拟。结果表明:本模拟所选用的数学模型及方法能比较合理地反映污泥颗粒絮凝-沉降过程的变化规律,并且具有一定精度;在固定水深处小粒径絮团数量随时间的推移不断减少,大粒径絮团数量随时间的推移先增加后减少,但是随着水深的增加污泥絮团的粒径分布范围逐渐变宽,大粒径污泥絮团的数量逐渐增多。展开更多
目的：验证通过非线性混合效应模型法（NONM EM ）软件建立的万古霉素群体药动学模型在神经外科重症患者中应用的有效性和实用性。方法回顾性收集2013年3月—2014年3月南京鼓楼医院神经外科重症加护病房中给予万古霉素治疗患者的性别、...目的：验证通过非线性混合效应模型法（NONM EM ）软件建立的万古霉素群体药动学模型在神经外科重症患者中应用的有效性和实用性。方法回顾性收集2013年3月—2014年3月南京鼓楼医院神经外科重症加护病房中给予万古霉素治疗患者的性别、年龄、体重、血肌酐和血白蛋白数值，通过前期建立的群体药动学模型，计算特定给药剂量下万古霉素的稳态血药谷浓度预测值，并与实际测量值比较，进而统计学分析验证。结果共收集患者42例，测得万古霉素血药谷浓度53份，平均谷浓度为10．9mg／L，范围为1．6～49．1mg／L。群体药动学模型的预测值与实际测量值有显著相关性（r＝0．857， P＜0．001），平均绝对百分比误差（MAPE）为0．4079，预测值的95％置信区间为9．36～14．07，实测值的95％置信区间为8．92～14．32。结论该群体药动学模型可以用于神经外科重症患者给予万古霉素前的预测和药物剂量的指导。但由于神经外科危重症患者昏迷，体重估计误差较大（约30％），同时对比剂和利尿药导致的肾功能改变影响结果。通过调整使用方法，预测准确率提高到近70％。展开更多
AIM: To establish a population pharmacokinetic/pharmacodynamic (PK/PD) model for valproate (VPA) in children with epilepsy in China, and promote reasonable use of antiepileptic drug in clinical practice. METHODS: Spar...AIM: To establish a population pharmacokinetic/pharmacodynamic (PK/PD) model for valproate (VPA) in children with epilepsy in China, and promote reasonable use of antiepileptic drug in clinical practice. METHODS: Sparse data of VPA serum concentrations from 417 pediatric children were collected. These patients were divided into three groups: Population PK-Index group, n=317; Population PK-Valid group, n=100; 115 of the total 417 subjects were also included in the Population PD group. Population PK parameters of VPA were estimated based on the data from population PK-Index group. In the validation procedure, the serum concentrations of VPA from the population PK-Valid group were predicted by base and final models respectively. To assess the accuracy and precision of the predictions, mean prediction error (MPE), mean squared prediction error (MSPE), root mean squared prediction error (RMSPE), weight-residues (WRES) and its 95% confidence intervals (95%CI) were all calculated, then compared between the two models. For population PD group, all of the 115 patients were VPA monotherapy. Efficacy of epilepsy treatment was divided into 5 grades according to the percentage of seizure frequency decreased (PSFD%). The value of PSFD% 100%, 75%-100%, 50%-75%, 25%-50%, or less than 25% are corresponding to grade 1 to 5. For population PD group, the quantitative relationship between the VPA serum concentrations and the probability for its efficacy score was characterized by logistic regression. RESULTS: Population PK of VPA was described by one-compartment model with first order absorption. In the final model, Ka, V/F, CL/F are 0.251+2.24·(1-HS) (/h), 2.88+0.157·WT (L), 0.1060.98·CO+0.0157·AGE (L/h), respectively. The final model was validated internally and externally. Logistic regression showed that VPA serum concentrations and corresponding peak probability for its efficacy were (25 μg/mL, grade 5, 50%), (32 μg/mL, grade 4, 32.3%), (50 μg/mL, grade 3, 26.3%), (67 μg/mL, grade 2, 36.5%), and (78 μg/mL, grade 1, 50%), respectively. CONCLUSION: The population PK/PD model of VPA in children with epilepsy in China is successfully established by NONMEM, and the probability of efficacy for a given concentration is satisfactorily estimated as well.展开更多
文摘针对在实验室中观测污泥絮凝-沉降过程及污泥颗粒絮团粒径分布情况存在盲点的问题,运用群平衡体模型(PBM)定义污泥颗粒的的尺寸,通过Lou模型与Ghadiri模型分别模拟污泥颗粒间的聚合及破碎机理,耦合PBM及两相流混合模型对Jeriffa De Clercp等在沉降桶内的污泥沉降实验进行三维数值模拟。结果表明:本模拟所选用的数学模型及方法能比较合理地反映污泥颗粒絮凝-沉降过程的变化规律,并且具有一定精度;在固定水深处小粒径絮团数量随时间的推移不断减少,大粒径絮团数量随时间的推移先增加后减少,但是随着水深的增加污泥絮团的粒径分布范围逐渐变宽,大粒径污泥絮团的数量逐渐增多。
文摘目的：验证通过非线性混合效应模型法（NONM EM ）软件建立的万古霉素群体药动学模型在神经外科重症患者中应用的有效性和实用性。方法回顾性收集2013年3月—2014年3月南京鼓楼医院神经外科重症加护病房中给予万古霉素治疗患者的性别、年龄、体重、血肌酐和血白蛋白数值，通过前期建立的群体药动学模型，计算特定给药剂量下万古霉素的稳态血药谷浓度预测值，并与实际测量值比较，进而统计学分析验证。结果共收集患者42例，测得万古霉素血药谷浓度53份，平均谷浓度为10．9mg／L，范围为1．6～49．1mg／L。群体药动学模型的预测值与实际测量值有显著相关性（r＝0．857， P＜0．001），平均绝对百分比误差（MAPE）为0．4079，预测值的95％置信区间为9．36～14．07，实测值的95％置信区间为8．92～14．32。结论该群体药动学模型可以用于神经外科重症患者给予万古霉素前的预测和药物剂量的指导。但由于神经外科危重症患者昏迷，体重估计误差较大（约30％），同时对比剂和利尿药导致的肾功能改变影响结果。通过调整使用方法，预测准确率提高到近70％。
文摘AIM: To establish a population pharmacokinetic/pharmacodynamic (PK/PD) model for valproate (VPA) in children with epilepsy in China, and promote reasonable use of antiepileptic drug in clinical practice. METHODS: Sparse data of VPA serum concentrations from 417 pediatric children were collected. These patients were divided into three groups: Population PK-Index group, n=317; Population PK-Valid group, n=100; 115 of the total 417 subjects were also included in the Population PD group. Population PK parameters of VPA were estimated based on the data from population PK-Index group. In the validation procedure, the serum concentrations of VPA from the population PK-Valid group were predicted by base and final models respectively. To assess the accuracy and precision of the predictions, mean prediction error (MPE), mean squared prediction error (MSPE), root mean squared prediction error (RMSPE), weight-residues (WRES) and its 95% confidence intervals (95%CI) were all calculated, then compared between the two models. For population PD group, all of the 115 patients were VPA monotherapy. Efficacy of epilepsy treatment was divided into 5 grades according to the percentage of seizure frequency decreased (PSFD%). The value of PSFD% 100%, 75%-100%, 50%-75%, 25%-50%, or less than 25% are corresponding to grade 1 to 5. For population PD group, the quantitative relationship between the VPA serum concentrations and the probability for its efficacy score was characterized by logistic regression. RESULTS: Population PK of VPA was described by one-compartment model with first order absorption. In the final model, Ka, V/F, CL/F are 0.251+2.24·(1-HS) (/h), 2.88+0.157·WT (L), 0.1060.98·CO+0.0157·AGE (L/h), respectively. The final model was validated internally and externally. Logistic regression showed that VPA serum concentrations and corresponding peak probability for its efficacy were (25 μg/mL, grade 5, 50%), (32 μg/mL, grade 4, 32.3%), (50 μg/mL, grade 3, 26.3%), (67 μg/mL, grade 2, 36.5%), and (78 μg/mL, grade 1, 50%), respectively. CONCLUSION: The population PK/PD model of VPA in children with epilepsy in China is successfully established by NONMEM, and the probability of efficacy for a given concentration is satisfactorily estimated as well.
