AbstractObserved rates of absorption of drugs by passive diffusion through lipid membranes depend on certain physicochemical properties of the drug being absorbed and of the lipid barrier to be penetrated. By combining the pH partition theory, the unstirred layer hypothesis, and LFE considerations several model equations were derived. Within congeneric series of acidic or basic compounds these equations allow one to quantitatively describe the nonlinear dependence of the rate of absorption on lipophilicity and degree of ionization as well as to explain the observation of pH shifts in pH absorption profiles of drugs. Generally an excellent fit of the equations to observed rate constants for several classes of compounds was obtained. Furthermore some indications are presented that absorption rates are influenced by aqueous as well as by lipid stagnant diffusion layers adjacent to the aqueous/lipid interface.