STUDIES OF HUMAN INTESTINAL ESTERASE .4. APPLICATION TO THE DEVELOPMENT OF ESTER PRODRUGS OF SALICYLIC-ACID

Esterase purified from human intestinal mucosa was investigated for its substrate specificity. Then the intestinal esterase was applied to the development of salicylic acid derivatives as prodrugs. The purified esterase hydrolyzed ester-type drugs. In all tested estertype drugs, aspirin was hydrolyzed most rapidly. So, the esters of salicylic acid were chosen as prodrugs. The purpose of this study was to seek salicylic acid derivatives as prodrugs which would be nonirritant, rapidly absorbed, and rapidly hydrolyzed. In the studies of hydrolysis of the esters of salicylic acid by the purified intestinal esterase and hepatic esterase, the esters were cleaved after absorption to exert their pharmacological activities due to the resultant salicylate. Of all synthesized esters, n-heptanoylsalicylic acid proved to be the most effective prodrug, because it exhibits higher analgesic activity, and its pharmacological profiles is quantitatively similar to that of aspirin. Besides, the acute toxicity and the gastric irritation potential of n-heptanoylsalicylic acid are less than those of aspirin. © 1979, The Pharmaceutical Society of Japan. All rights reserved.