COMPARISON OF ENZYMATIC-ACTIVITIES OF TISSUES LINING PORTALS OF DRUG ABSORPTION, USING THE RAT AS A MODEL

Leucine aminopeptidase and cholesteryl esterase activities of five different tissues from the rat are investigated. The tissues from the intestines, the buccal cavity, the nose, the rectum and the skin were chosen, as they represent barriers to absorption for most commonly used dosage forms. It is shown that the intestinal tissue is the most active in both enzymes. Dermal tissues are the second richest in cholesteryl esterase activity, whereas rectal tissue is the least active. Aminopeptidase activity is weakest in dermal tissues. When adjusted for protein content, dermal tissues show the highest specific esterase activity. Rectal tissue remains the least active. Based on the known relatively high permeability of buccal and nasal tissues, the low aminopeptidase and cholesterol esterase activities would suggest that those routes offer better possibilities for delivering peptides and esters. However, it should be noted that enzymic degradation is only one of the barriers to peptide absorption, and for most peptide drugs an absorption enhancer or a specific delivery system is still likely to be required for successful trans-nasal or buccal absorption. © 1990.