Fig. 4
Plasma and brain tissue binding, unbound volume of distribution, and cellular partitioning in rat tissue. A Schematic illustration of the principle behind equilibrium dialysis. Only unbound drug (Cunbound) can penetrate the semipermeable membrane allowing estimation of the extent of drug tissue binding at equilibrium. B The fu,plasma of eletriptan and sumatriptan assessed at 200 nM (n = 3, N = 3). C The fu, brain eletriptan and sumatriptan in brain homogenate assessed at 1 µM (n = 3, N = 3). D Schematic illustration of the principle behind Vu,brain. The distribution of unbound drug from artificial extracellular fluid (aECF), which mimics brain ISF, into the ICF of brain parenchymal cells allows for transmembrane pH gradients, also enabling lysosomal trapping. E The Vu,brain of eletriptan and sumatriptan (100 nM) in rat brain slices (n = 3, N = 5). F Schematic illustration of the principle behind Kp, uu, cell. G Estimated Kp, uu, cell of eletriptan and sumatriptan at equilibrium. In Fig. 4G, the dotted line represents the line of unity. Each column represents mean ± SD. The groups were compared using a student’s two-tailed t-test (n = 3, N = 5). Created with Biorender.com