We previously reported a classical quantitative structure–activity relationship (QSAR) equation for permeability coefficients ( P app-pampa) by parallel artificial membrane permeation assay (PAMPA) of structurally diverse compounds with simple physicochemical parameters, hydrophobicity at a particular pH (log P oct and |p K a − pH|), hydrogen-accepting ability ( SA HA), and hydrogen-donating ability ( SA HD); however, desipramine, imipramine, and testosterone, which have high log P oct values, were excluded from the derived QSAR equation because their measured P app-pampa values were lower than calculated. In this study, for further investigation of PAMPA permeability of hydrophobic compounds, we experimentally measured the P app-pampa of more compounds with high hydrophobicity, including several pesticides, and compared the measured P app-pampa values with those calculated from the QSAR equation. As a result, compounds having a calculated log P app-pampa > −4.5 showed lower measured log P app-pampa than calculated because of the barrier of the unstirred water layer and the membrane retention of hydrophobic compounds. The bilinear QSAR model explained the PAMPA permeability of the whole dataset of compounds, whether hydrophilic or hydrophobic, with the same parameters as the equation in the previous study. In addition, PAMPA permeability coefficients correlated well with Caco-2 cell permeability coefficients. Since Caco-2 cell permeability is effective for the evaluation of human oral absorption of compounds, the proposed bilinear model for PAMPA permeability could be useful for not only effective screening for several drug candidates but also the risk assessment of chemicals and agrochemicals absorbed by humans.