Beyond the Blood: Brain Barrier: The Importance of Central Nervous System (CNS) Pharmacokinetics for the Treatment of CNS Tumors, Including Diffuse Intrinsic Pontine Glioma

被引:139
作者
Warren, Katherine Elizabeth [1 ]
机构
[1] NCI, Neurooncol Sect, Pediat Oncol Branch, Rockville, MD 20850 USA
基金
美国国家卫生研究院;
关键词
central nervous system pharmacokinetics; blood: brain barrier; brain tumor; diffuse intrinsic pontine glioma; drug delivery; CEREBROSPINAL-FLUID PHARMACOKINETICS; HIGH-DOSE-CHEMOTHERAPY; STEM GLIOMAS; RADIATION-THERAPY; NONHUMAN-PRIMATES; EXTRACELLULAR-SPACE; ARTERIAL INFUSIONS; CYCLOSPORINE-A; ONCOLOGY-GROUP; DRUG-DELIVERY;
D O I
10.3389/fonc.2018.00239
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Over the past decade, we have made considerable progress in establishing diffuse intrinsic pontine glioma (DIPG) as a disease entity and developing preclinical tools to interrogate potential therapeutics. However, translation to improved clinical outcomes in children with DIPG has not yet been realized. This is in part due to difficulties encountered in delivering active drugs adequately to the tumor site. However, most preclinical evaluations gloss over the fundamental concepts of central nervous system (CNS) pharmacokinetics and requirements needed to optimize drug delivery and exposure and translate this into efficacious therapy. This article discusses not only the blood: brain barriers but additional barriers to drug delivery for CNS tumors and pharmacokinetic principles that need to be addressed and considered.
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页数:11
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