Predicting tacrolimus concentrations in children receiving a heart transplant using a population pharmacokinetic model.
Predicting tacrolimus concentrations in children receiving a heart transplant using a population pharmacokinetic model.
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DOI：
10.1136/bmjpo-2017-000147
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发表时间：
2017
影响因子：
2.6
通讯作者：
Molina KM
中科院分区：
文献类型：
--
作者：
Rower JE;Stockmann C;Linakis MW;Kumar SS;Liu X;Korgenski EK;Sherwin CMT;Molina KM
免疫抑制剂治疗在移植成功和长寿中起着关键作用。他克莫司，一种主要的免疫抑制剂，是众所周知的，表现出显着的药理学患者间和患者内的差异。这种变异性需要收集系列谷浓度，以确保药物保持在治疗范围内。本研究的目的是建立群体药代动力学（PK）模型，并使用该模型确定指导预测个体未来浓度所需的最少谷值样本数量。本研究纳入了来自犹他湖城初级儿童医院48名接受他克莫司治疗的住院儿童的回顾性数据。在心脏移植后的前6周内收集数据。数据分析使用NONMEM中的群体PK建模技术。使用中位数预测误差（MPE，偏差的量度）和中位数绝对预测误差（MAPE，准确度的量度）确定模型的预测能力。在研究中的48名儿童中，30名用于模型构建数据集，18名用于模型验证数据集。在所有收集的数据中，浓度范围为1.5至37.7 µg/L，其中只有40%的浓度在目标浓度范围（12至16 µg/L）内。最终群体PK模型包含年龄（对体积）、肌酐清除率（对消除率）和氟康唑使用（对消除率）作为协变量的影响。我们的分析表明，只需三种浓度就可以用于预测未来的浓度，偏差可以忽略不计（MPE（95% CI）=0.10%（-2.9%至3.7%）），准确性良好（MAPE（95% CI）=24.1%（19.7%至27.7%））。在剂量指导中使用PK有可能为临床护理提供显著益处，包括在治疗早期阶段进行剂量优化，并有可能限制频繁药物监测的需求。
Immunosuppressant therapy plays a pivotal role in transplant success and longevity. Tacrolimus, a primary immunosuppressive agent, is well known to exhibit significant pharmacological interpatient and intrapatient variability. This variability necessitates the collection of serial trough concentrations to ensure that the drug remains within therapeutic range. The objective of this study was to build a population pharmacokinetic (PK) model and use it to determine the minimum number of trough samples needed to guide the prediction of an individual’s future concentrations. Retrospective data from 48 children who received tacrolimus as inpatients at Primary Children’s Hospital in Salt Lake City, Utah were included in the study. Data were collected within the first 6 weeks after heart transplant. Data analysis used population PK modelling techniques in NONMEM. Predictive ability of the model was determined using median prediction error (MPE, a measure of bias) and median absolute prediction error (MAPE, a measure of accuracy). Of the 48 children in the study, 30 were used in the model building dataset, and 18 in the model validation dataset. Concentrations ranged between 1.5 and 37.7 µg/L across all collected data, with only 40% of those concentrations falling within the targeted concentration range (12 to 16 µg/L). The final population PK model contained the impact of age (on volume), creatinine clearance (on elimination rate) and fluconazole use (on elimination rate) as covariates. Our analysis demonstrated that as few as three concentrations could be used to predict future concentrations, with negligible bias (MPE (95% CI)=0.10% (−2.9% to 3.7%)) and good accuracy (MAPE (95% CI)=24.1% (19.7% to 27.7%)). The use of PK in dose guidance has the potential to provide significant benefits to clinical care, including dose optimisation during the early stages of therapy, and the potential to limit the need for frequent drug monitoring.
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DOI：
10.1016/j.healun.2011.08.001
发表时间：
2011-12
期刊：
The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation
影响因子：
--
作者：
Gijsen V;Mital S;van Schaik RH;Soldin OP;Soldin SJ;van der Heiden IP;Nulman I;Koren G;de Wildt SN
通讯作者：
de Wildt SN
影响因子：
3.4
作者：
Jalil, Mariam H. Abdel;Hawwa, Ahmed F.;McElnay, James C.
通讯作者：
McElnay, James C.
影响因子：
19.6
作者：
Scholten, EM;Cremers, SCLM;de Fijter, JW
通讯作者：
de Fijter, JW
影响因子：
4.5
作者：
Benkali, Khaled;Rostaing, Lionel;Rousseau, Annick
通讯作者：
Rousseau, Annick
影响因子：
3.3
作者：
Okabe, H;Yano, I;Inui, KI
通讯作者：
Inui, KI