ABSTRACT
Combinatorial synthesis and high-throughput pharmacology screening have greatly increased compound throughput in modern drug-discovery programs. For CNS drugs, it is also important to determine permeability to the blood--brain barrier. Yet, given the increased pace of discovery, it difficult to conduct this screen in a timely fashion. In this presentation, we describe several improvements to an existing CNS permeability screen, the bovine brain microvessel endothelial cell (BBMEC) model. By implementation of these incremental process improvements, we have achieved a robust, facile screen for determination of CNS permeability of multiple compounds.
Subject(s)
Blood-Brain Barrier , Brain/blood supply , Drug Evaluation, Preclinical/methods , Endothelium, Vascular/metabolism , Animals , Antineoplastic Agents, Phytogenic/pharmacokinetics , Biological Transport , Caffeine/pharmacokinetics , Cattle , Central Nervous System Agents/pharmacokinetics , Drug Combinations , Mannitol/pharmacokinetics , Microdialysis , Models, Biological , Permeability , Vinblastine/pharmacokineticsABSTRACT
Experimental models that have application for evaluating enzyme induction potential have been described in order of increasing complexity. The main focus was on models that have had wide application thus far. However, many new models are currently being developed that may have future applications in evaluating enzyme induction potential. A strategy to evaluate the enzyme induction potential of drug candidates was outlined. This scheme uses a combination of new and established techniques to evaluate data in a stepwise manner that is appropriate to the drug's current stage of development.