Evaluation of the BBMEC model for screening the CNS permeability of drugs.
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.
Otis
K W
KW
Quintiles Inc., PO Box 9708, Kansas City, MO 64134, USA. tom.thompson@quintiles.com
Avery
M L
ML
Broward-Partin
S M
SM
Hansen
D K
DK
Behlow
H W
HW
Scott
D O
DO
Thompson
T N
TN
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000493:pharmacokinetics; D001692:Biological Transport; D001812:Blood-Brain Barrier; D001921:Brain / Q000098:blood supply*; D002110:Caffeine / Q000493:pharmacokinetics; D002417:Cattle; D002491:Central Nervous System Agents / Q000493:pharmacokinetics; D004338:Drug Combinations; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D004730:Endothelium, Vascular / Q000378:metabolism*; D008353:Mannitol / Q000493:pharmacokinetics; D017551:Microdialysis; D008954:Models, Biological; D010539:Permeability; D014747:Vinblastine / Q000493:pharmacokinetics
D000972:Antineoplastic Agents, Phytogenic; D002491:Central Nervous System Agents; D004338:Drug Combinations; D002110:Caffeine; D008353:Mannitol; D014747:Vinblastine