Brain drug delivery, drug metabolism, and multidrug resistance at the choroid plexus

The choroid plexuses (CPs) have the capability to modulate drug delivery to the cerebrospinal fluid (CSF) and to participate in the overall cerebral b iodisposition of drugs. The specific morphological properties of the choroi dal epithelium and the existence of a CSF pathway for drug distribution to different targets in the central nervous system suggest that the CP-CSF rou te is more significant than previously thought for brain drug delivery. In contrast to its role in CSF penetration of drugs, CP is also involved in br ain protection in that it has the capacity to clear the CSF from numerous p otentially harmful CSF-borne exogenous and endogenous organic compounds int o the blood. Furthermore, CP harbors a large panel of drug-metabolizing enz ymes as well as transport proteins of the multidrug resistance phenotype, w hich modulate the cerebral bioavailability of drugs and toxins. The use of an in vitro model of the choroidal epithelium suitable for drug transport s tudies has allowed the demonstration of the choroidal epithelium acting as an effective metabolic blood-CSF barrier toward some xenobiotics, and that a vectorial, blood-facing efflux of conjugated metabolites occurs at the ch oroidal epithelium. This efflux involves a specific transporter with charac teristics similar to those of the multidrug resistance associated protein ( MRP) family members. Indeed, at least one member, MRP1, is largely expresse d at the CP epithelium, and localizes at the basolateral membrane. These me tabolic and transport features of the choroidal epithelium point out the CP as a major detoxification site within the brain. (C) 2001 Wiley-Liss, Inc.