Kinetic analysis of drug transport in the brain

Abstract

In order to understand dynamically the drug transport and disposition in the brain, it is important to obtain the kinetic parameters representing the individual rate process. The rate processes which should be considered are influx from blood to brain, efflux from CSF (or brain) to blood, diffusion in extracellular space, exchange between intracellular space and extracellular space, and intracellular binding and metabolism. In this minireview, several methods to obtain the influx and efflux rate constants were summarized and the advantages and limitations of each method were discussed. The methods include not only in vivo and in situ methods but also in vitro experimental system using isolated microvessel (brain capillary) and choroid plexus which might possibly be suitable for screening the influx and efflux permeability of drugs, respectively. Of most importance finally is to construct a kinetic model to predict the time course of drug concentrations in various regions of brain by incorporating thus obtained kinetic parameters. The concepts developed in the field of physiological pharmacokinetic modeling might be helpful to fulfill this purpose.