Projecting large animal unbound brain compound concentrations

2 Projecting large animal unbound brain compound concentrations 

Based on rat neuropharmacokinetic concepts, it has been proposed [37,42,45] that Cb/U may be projected directly from Cp for large animal species (i.e., dog, monkey, and human) in which Cb are rarely measured. For such species, in which serial blood sampling is common for determining plasma pharmacokinetics, compound Cb,u may be extrapolated using its Cp, species-specific /u,p, and rat-derived Cb,u CP/U assuming a fixed ratio across species  

A common cross-species Cb,u CP/11 is not universal as occasionally compounds are found to have different degrees of cross-species CNS penetration due to reasons ranging from species differences in P-gp transport to variable intrabrain distribution [46]. However, for compounds in which brain penetration is predominately mediated by passive diffusion, such species differences are more often the exception than the rule. Finally, this methodology implies that a compound s /u b is identical 

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