Applications of a blood-brain barrier technology platform to predict CNS penetration of various chemotherapeutic agents. 1. Anti-infective drugs.

Except for a few well-documented CNS therapeutics, quantitative data on blood-brain barrier (BBB) permeation is incomplete, unreliable or nonexistent and this is a major impediment in BBB modeling. Furthermore, only the passive diffusion component is generally taken into account. Three techniques of modeling (in vivo, in vitro and in silico) were set up and compared. The in silico predicted permeation of 287 anti-infective drugs has been faced to clinical observations. Good correlations were observed between in vitro permeability coefficients, influx transfer coefficients from in vivo studies and Pe scores from the computational model. High Pe score values are associated with an increase of reported CNS side effects.