To clarify sotalol's classification in the BCS versus BDDCS systems through cellular, rat everted sac and PAMPA permeability studies. Studies were carried out in Madin Darby canine kidney (MDCK) and MDR1-transfected MDCK (MDCK-MDR1) cell lines, rat everted gut sacs and the Parallel Artificial Membrane Permeability Assay (PAMPA) system. Three-hour transport studies were conducted in MDCK cell lines (with apical pH changes) and MDCK-MDR1 cells (with and without the P-glycoprotein inhibitor GG918); male Sprague-Dawley rats (300~350g) were used to prepare everted sacs. In the PAMPA studies, drug solutions at different pH's were dosed in each well and incubated for 5h. Samples were measured by LC-MS/MS, or liquid scintillation counting and apparent permeability (P(app)) was calculated. Sotalol showed low permeability in all of the cultured-cell lines, everted sacs and PAMPA systems. It might be a border line P-glycoprotein substrate. The PAMPA study showed that sotalol's permeability increased with a higher apical pH, while much less change was found in MDCK cells. The low permeability rate for sotalol correlates with its Class 3 BDDCS assignment and lack of in vivo metabolism.