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Effect of simultaneous administration of drugs on absorption and excretion. VI. Effect of protein binding on membrane permeability of sulfonamides.

Effect of protein binding on permeation of sulfonamides through a cellophane membrane was investigated by use of a dynamic dialysis technique. The membrane permeation of sulfadimethoxine and sulfamethoxypyridazine that showed high binding to bovine serum albumin (BSA) was significantly increased by the presence of BSA in the receptor compartment, while the membrane permeation of sulfanilamide that showed little binding to BSA was not changed at all by the presence of BSA. Further the increase in the membrane permeation of sulfadimethoxine and sulfamethoxypyridazine in the presence of BSA was significantly depressed by the addition of salicylic acid. Also, salicylic acid strongly displaced sulfadimethoxine or sulfamethoxypyridazine from its protein binding sites. These results suggest that the depressive effect of salicylic acid on the membrane permeation of sulfadimethoxine and sulfamethoxypyridazine in the presence of BSA is due to its displacing activity.