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Molecular Pharmacology, Vol 1, 266-279, Copyright © 1965 by the American Society for Pharmacology and Experimental Therapeutics

Diffusion of Sulfonamides in Aqueous Buffers and into Red Cells

LARRY B. HOLDER 1 and SHERRARD L. HAYES 1

1 Department of Pharmacology and Therapeutics, University of Florida College of Medicine, Gainesville, Florida

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.

Note:
ACKNOWLEDGMENT We would like to express appreciation to Dr. Thomas H. Maren for his many constructive suggestions and much kind assistance. Supported by National Institutes of Health Research Grant NB-01297 and Training Grant GM 760. The work is part of the Student Research Program in the Medical Curriculum and the Training Program in Pharmacology.

Submitted on September 13, 1965




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