脑肿瘤治疗缺乏有效的化疗药物是一个严重尚未满足的医疗需求。这部分归因于通过血脑屏障（BBB）和肿瘤细胞屏障的不足递送，两者均具有能限制许多潜在有效药物运输的活性外排转运体，适用于原发性和转移性脑肿瘤。该综述简要总结了正常BBB的组分和功能，以及与药物穿透脑部有关的BBB的改变和对药物递送的影响。根据化合物的分布限制，BBB的有限渗透性和随后的药物递送到肿瘤细胞可受到活性外排转运体的显著影响，这些部分将从某些详细方面进行讨论。鉴于这些复杂性，有必要量化活性（非结合）药物在脑部的分布范围，以对比各种化合物，并为对抗脑肿瘤的潜力提供信息。在这方面，脑血浆非结合分配系数（Kp,uu）是一种指标，其目前的使用情况进行了讨论。然而，活性药物递送的程度并不是有效治疗的唯一决定因素。除了Kp,uu之外，药物的效力也是在药物发现和开发过程中应考虑的重要参数。换句话说，要回答“多少才够？”的问题，必须考虑能够递送多少以及需要递送多少。©2023. Springer Science+Business Media, LLC独家许可，Springer Nature的一部分。

The lack of effective chemotherapeutic agents for the treatment of brain tumors is a serious unmet medical need. This can be attributed, in part, to inadequate delivery through the blood-brain barrier (BBB) and the tumor-cell barrier, both of which have active efflux transporters that can restrict the transport of many potentially effective agents for both primary and metastatic brain tumors. This review briefly summarizes the components and function of the normal BBB with respect to drug penetration into the brain and the alterations in the BBB due to brain tumor that could influence drug delivery. Depending on what is rate-limiting a compound's distribution, the limited permeability across the BBB and the subsequent delivery into the tumor cell can be greatly influenced by efflux transporters and these are discussed in some detail. Given these complexities, it is necessary to quantify the extent of brain distribution of the active (unbound) drug to compare across compounds and to inform potential for use against brain tumors. In this regard, the metric, Kp,uu, a brain-to-plasma unbound partition coefficient, is examined and its current use is discussed. However, the extent of active drug delivery is not the only determinant of effective therapy. In addition to Kp,uu, drug potency is an important parameter that should be considered alongside drug delivery in drug discovery and development processes. In other words, to answer the question - How much is enough? - one must consider how much can be delivered with how much needs to be delivered.© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.