Dose adjustment in orphan disease populations: the quest to fulfill the requirements of physiologically based pharmacokinetics
Dose adjustment in orphan disease populations: the quest to fulfill the requirements of physiologically based pharmacokinetics
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孤儿疾病人群的剂量调整：寻求满足基于生理的药代动力学的要求
DOI：
10.1080/17425255.2018.1546288
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发表时间：
2018
影响因子：
4.3
通讯作者：
A. Rostami
中科院分区：
文献类型：
--
作者：
Martyn Howard;J. Barber;N. Alizai;A. Rostami
摘要简介：当媒体被“精准医疗”的概念所吸引时，与“精准剂量”相关的细微差别似乎在很大程度上被忽视了。假设选择了“正确的药物”，临床医生仍然需要决定个人的“正确剂量”。理想情况下，应在临床试验中研究最佳剂量；然而，市场上的许多药物缺乏基于证据的剂量建议，并且一小部分患者（孤儿病人群）依赖当地指导和临床医生的经验来确定药物剂量调整。涵盖领域：本报告探讨了目前对特殊人群剂量调整的理解，并检查了为儿科、老年人和孕妇患者开发“计算机化”模型的要求。该报告还强调了在孤儿病人群缺乏完整临床试验的情况下，目前使用模型为药物标签提供循证建议。专家意见：基于生理的药代动力学（PBPK）在确定特殊人群的最佳药物剂量调整方面具有诱人的前景。然而，除非获得建立稳健的PBPK模型所需的系统（与药物无关）数据，否则这对于个体化甚至分层给药是不够的。这些模型不能替代临床试验，但它们可以替代未记录的和不一致的猜测。
ABSTRACT Introduction: While the media is engaged and fascinated by the idea of ‘Precision Medicine’, the nuances related to ‘Precision Dosing’ seem to be largely ignored. Assuming the ‘right drug’ is selected, clinicians still need to decide on the ‘right dose’ for individuals. Ideally, optimal dosing should be studied in clinical trials; however, many drugs on the market lack evidence-based dosing recommendations, and small groups of patients (orphan disease populations) are dependent on local guidance and clinician experience to determine drug dosage adjustments. Areas Covered: This report explores the current understanding of dosing adjustment in special populations and examines the requirements for developing ‘in silico’ models for pediatric, elderly and pregnant patients. The report also highlights current use of modeling to provide evidence-based recommendations for drug labeling in the absence of complete clinical trials in orphan disease populations. Expert Opinion: Physiologically based pharmacokinetics (PBPK) is an attractive prospect for determining the best drug dosage adjustments in special populations. However, it is not sufficient for individualized, or even stratified dosing, unless the systems (drug-independent) data required to build robust PBPK models are obtained. Such models are not a substitute for clinical trials, but they are an alternative to undocumented and inconsistent guesswork.
影响因子：
2.3
作者：
Gandhi A;Moorthy B;Ghose R
通讯作者：
Ghose R
影响因子：
2.3
作者：
Pinto N;Dolan ME
通讯作者：
Dolan ME
影响因子：
3.8
作者：
Divakaran, Karthika;Hines, Ronald N.;McCarver, D. Gail
通讯作者：
McCarver, D. Gail