Studies of human intestinal esterase. IV. Application to the development of ester prodrugs of salicylic acid.

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Abstract
Esterase purified from human intestinal mucosa was investigated for its substrate specificity. The intestinal esterase was applied to the development of salicylic acid derivatives as prodrugs. The purified esterase hydrolyzed ester-type drugs. Since aspirin was hydrolyzed most rapidly 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 salicylic acid ester hydrolysis by purified intestinal esterase and hepatic esterase, the esters were cleaved after absorption. The resultant salicylate was pharmacologically active. n-Heptanoylsalicylic acid proved to be the most effective prodrug because it exhibits higher analgesic activity and quantitatively similar pharmacological profiles to those of aspirin. The acute toxicity and the gastric irritation potential of n-heptanoylsalicylic acid are also less than those of aspirin.