Intestinal Handling of Bisacodyl and Picosulphate by Everted Sacs of the Rat Jejunum and Stripped Colon

Abstract

Bisacodyl (BIS) is the acetic acid di‐ester of the laxative diphenol 2‐(4,4′‐dihydroxydiphenyl)methylpyridine. A HPLC‐method which permits the simultaneous determination of BIS and its monodesacetylated (MONO) as well as totally desacetylated (DES) form, has been used to study the intestinal handling of BIS (20 nmol/ml), when the compound was incubated for 60 min. at the mucosal side of the preparations specified. In the jejunal mucosal fluid, BIS disappeared completely in short time, and there was a nearly equivalent rise in DES. MONO was transitory present. Hydrolysis was also rapid in mucosal fluid which had been in contact with jejunal sacs for 30 sec., but BIS was stable in blank incubations. Hydrolysis of BIS was slower by colonic than by jejunal sacs, and all three molecular forms were present during incubation. It seemed still slower in mucosal fluid which had been in contact with colonic sacs for 5 min. BIS just as DES accumulated in the jejunal and colonic serosal fluid mainly as conjugates (>95%), and DES was in all cases the only unconjugated metabolite present. Drug accumulation in jejunal serosal fluid was the same whether BIS or DES was added. However, more drug seemed to accumulate on the serosal side of colonic sacs when incubated with BIS instead of DES. In similar experiments with picosulphate, which is the sulphuric acid di‐ester analogue of BIS, free DES was not detected in the mucosal fluid during incubation. The amounts of laxative accumulating in the serosal fluid were less than 1/10 of those observed with BIS.

Uptake, Conjugation and Transport of Laxative Diphenols by Everted Sacs of the Rat Jejunum and Stripped Colon

“…, 1981Sund e t al. & 1982Hillestad et al 1982) that the exposure of the target cells, i.e. the colonic enterocytes and hence laxative effect, will depend on the balance between 5 main processes, viz.…”