Introduction

Measurement of brain uptake rates after intravenous (i.v.) administration of a test substance followed by sampling of brain tissue has been the most widely used approach compared to other techniques for measuring the permeability of the blood–brain barrier (BBB). In contrast to single-passage methods such as the brain uptake index (BUI) and to the indicator dilution technique, brain uptake in i.v. experiments is measured after multiple passages through the capillary bed and offers the highest potential sensitivity of the available techniques. However, the apparent experimental simplicity may mislead the investigator about the fact that the obtained data are readily misinterpreted. Awareness of potential pitfalls associated with the method is required to avoid mistakes in the experimental protocol and evaluation that could distort the results. The purpose of this chapter is to briefly introduce aspects of pharmacokinetic evaluations and highlight specific advantages and disadvantages of the intravenous approach, with examples.

Technically, measurement of brain uptake typically involves injection of the test compound as a radiolabeled tracer in physiological solution as an i.v. bolus. Radiolabeling is not required if sufficiently sensitive analytical methods are available for measuring the substance under investigation in plasma and tissue. Corresponding to the species in which the study is performed, the injected volume should be sufficiently small compared to the total intravascular volume not to introduce a systematic error.