Introduction

Brain interstitial fluid concentration of drugs and/or nutrients, a significantly important value for the central nervous system (CNS) effects and/or the cerebral functions, is believed to be mainly governed by the net flux between the brain interstitial fluid and the circulating blood in the brain capillaries across the blood–brain barrier (BBB). Although several influx transport systems at the BBB have been characterized (Pardridge and Oldendorf, 1977; Pardridge, 1983; Smith et al., 1987; Terasaki et al., 1991), only a limited amount of information appears to be available on the transport process from the brain interstitial fluid to the circulating blood at the BBB (Betz and Goldstein, 1978; Oldendorf et al., 1982; Barrera et al., 1991; Banks et al., 1993), i.e. the BBB efflux transport process. For an understanding of the physiological function of the BBB, presumably as a regulating machinery of brain interstitial fluid constituents balance including nutrients, neurotransmitters and its metabolites, it is significantly important to clarify the efflux transport process across the BBB. Moreover, it would also be helpful for the development of the CNS-acting drugs to characterize the drug efflux transport process from the brain, while most studies have been focused on the influx process from the circulating blood to the brain. The purpose of this chapter is to describe the Brain Efflux Index (BEI) method, a newly developed method to determine the in vivo efflux transport clearance across the BBB (Kakee et al., 1996).