Brain–blood ratio: implications in brain drug delivery

Introduction: The brain–blood ratio is an important model correlating the brain-targeting ability of neurotherapeutics with the CNS pharmacokinetics, which need to be presented before the scientific community for exploration of its scientific worth. The purpose of this article is to bring this key concept and its precise discussion to the attention of the researchers.Areas covered: Three major points are discussed herein: First, the significance of brain–blood ratio with respect to investigational neurotherapeutics, and carrier systems and correlation of its research findings with the brain targeting efficiency. Second, the various factors influencing the brain–blood ratio. Third, the various strategies for enhancing the brain–blood ratio. In addition, the benchmark criteria for CNS-likeness of drug molecules and the correlation of brain–blood ratio with brain targeting ability of neurotherapeutics have been tabulated.Expert opinion: The brain–blood ratio (also referred to as the brain–plasma ratio) represents one of the tools available today for estimation of CNS pharmacokinetics. It is preferred over other complicated techniques (in situ brain perfusion and microdialysis) due to its ease of use and practicality. We are optimistic that the brain–blood ratio offers an excellent way of evaluating brain-targeting efficiency of neurotherapeutics effectively. In our opinion, it is a very fundamental aspect of brain bioavailability and needs to be presented in a precise way.