Studies in the rat on the absorption, biliary excretion, laxative action and interference with intestinal transport of some oxyphenisatin derivatives [bisacodyl, jejunum, colon]

The free diphenol oxyphenisatin (I) and its sulphuric acid (II) and acetic acid (III) di‐esters are compared. I disappered rapidly from the lumen of tied jejunal loops in vivo; its disapperance was associated with an inhibition of normal fluid absorption and an increase in loop tissue wet weight. II disappeared slowly, and did neither inhibit fluid absorption nor cause an increase in wet weight. Large fractions of I conjugates were excreted in the bile 0‐6, 6‐12 and 12‐18 hrs following intragastric administration of I; after II and III much smaller fractions were excreted, and their time pattern differed from that of I. The absorption and biliary excretion experiments when combined indicate that following intragastric administration in the intact rat, the bulk of I will undergo enterohepatic circulation during its small intestinal transit, while II and III pass largely unabsorbed to the colon. In spite of their direct transit, however, the laxative action of both II and III in concious rats was slower in onset than of I. In this respect, II differed strikingly from the sulphuric acid di‐ester of desacetyl‐bisacodyl (IV), which acted even more promptly than I. As in the jejunum, II was inactive per se in tied colonic loops; liberation of free I being required to elicite inhibition of colonic electrolyte and fluid absorption. The reason for the long laxative latency period of II and III appears then mainly to be slow colonic hydrolysis of these prodrugs. Supplementary experiments supported this view as far as the water soluble II is concerned, and slow hydrolysis is very likely for such a sparingly soluble drug as III.