Current in vitro and in silico models of blood-brain barrier penetration: a practical view.
Predictive, cost effective and fast evaluation of CNS penetration or unbound brain levels of NCEs, or both, presents a considerable challenge in preclinical screening in the pharmaceutical industry. It is evident that neither a single in vitro model nor a set of physicochemical parameters is capable of predicting complex in vivo measures, such as brain distribution or blood-brain barrier (BBB) penetration, accurately. Various in vitro and in silico strategies have been developed to model drug action as a function of BBB properties, with models that provide sufficient predictivity, reliability and throughput to be favored by the pharmaceutical industry. This review gives a practical summary of in vitro and in silico approaches to evaluate BBB penetration.
Vastag
Mónika
M
Gedeon Richter plc, Gyömroi út, Budapest, Hungary.
Keseru
György M
GM
D000818:Animals; D001812:Blood-Brain Barrier / Q000378:metabolism*; D002460:Cell Line; D015195:Drug Design; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D006801:Humans; D008954:Models, Biological; D010539:Permeability; D010599:Pharmacokinetics