Drug transport in the mammalian central nervous system: multiple complex systems. A critical analysis and commentary

Abstract

The rate of entry into and distribution of drugs and endogenous substances within the mammalian central nervous system (CNS) depend on the peculiar anatomy of the blood-brain and blood-cerebrospinal fluid barriers, the physicochemical nature of the substance or drug, and in many cases, multiple, complex specialized carriers. This review summarizes a systemic methodological and integrative approach to understanding the pharmacokinetic behavior of many drugs in the CNS in the context of the CNS barrier systems, focusing on recent data, several broad principles and selected examples. Standards of proof for valid conclusions are emphasized.