A high-throughput, UV-detection PAMPA (parallel artificial membrane permeability assay) cosolvent procedure is described, based on the use of 20% v/v acetonitrile in aqueous buffer. A training set of 32 drugs (17 bases, 13 acids, 2 ampholytes) was studied both in aqueous buffer and in cosolvent-buffer solutions. A procedure was devised, where intrinsic permeability values, log P_o^COS, measured in cosolvent solution, are converted to values expected under cosolvent-free conditions, using an in silico model based on Abraham H-bond acidity (α) and basicity (β) descriptors, developed with the Algorithm Builder computer program, to obtain aqueous intrinsic permeability values: log P_o=0.738+0.885 log P_o^COS−1.262α+0.436β, r²=0.97, q²=0.96, s=0.38, n=32, F=279. Five sparingly-soluble weak bases (solubility <1 μg/ml), which could not be characterized without cosolvent, had their aqueous intrinsic permeability, P_o, estimated: miconazole 0.32 cm/s; itraconazole 3.2 cm/s; amiodarone 13 cm/s; tamoxifen 28 cm/s; terfenadine 162 cm/s.