FIGURE 2.
(A) The Kin of R123 in the presence of the known P-gp inhibitors, cyclosporin A and verapamil, increases brain distribution (as reported by the Kin) by >10-fold. All data represent mean ± S.E.M for total brain; n = 3–5 for all groups. Statistics: one-way ANOVA; Dunnett’s. (B) The relationship between LogD (octanol/water coefficient; pH = 7.4) and observed Kin is used to profile a molecule or drug’s mechanism of distribution into brain. Compounds that are known to cross the BBB via passive diffusion are plotted using gray squares and those subject to efflux are plotted with gray triangles. R123 (open circle) falls below ~3 log units the line of identity for passive permeability indicating it may be subject to efflux.