Abstract

Diffusion characteristics of eight sulfonamides including five carbonic anhydrase inhibitors and three antibacterial drugs were studied in detail. There was very little variation in magnitudes of aqueous diffusion coefficients among the drugs.

The diffusivities into red cells were 10^-4 to 10^-8 those in aqueous medium. Drugs showed a range of 4000-fold in rates of red cell penetration. Lipid solubilities of the various drugs were approached by means of the CHCl₃:H₂O partition coefficients which covered a range of 2.5 x 10⁵. A diffusion constant for drugs into red cells was calculated using the square root of the lipid solubility; the range of penetration rates was thereby reduced from 4000 to 100.

All these drugs appeared to diffuse passively down a concentration gradient into the red cells. It was proposed that the rate-limiting step in the passage of these drugs into the red cell is at the cell membrane and that aqueous diffusion normally is of little significance in affecting the overall rates of penetration.

From penetration kinetics of sulfonamides into dog and human red cells, it was concluded that the two most important characteristics which influence these rates are plasma drug binding and lipid solubility, as measured at physiological pH.