Gastrointestinal absorption of quaternary ammonium compounds correlated to their binding to small intestinal brush border membrane in rat

Abstract

The relationship between absorption of quaternary ammonium compounds (QACs) from rat intestine and their in-vitro binding to isolated brush-border membrane has been examined, using a series of n-alkyltrimethylammoniums. The binding of these QACs gradually increased with each extension of unbranched hydrocarbon chain from octyltrimethylammonium to tetradecyltrimethylammonium. However, hexyltrimethylammonium and heptyltrimethylammonium failed to bind to the membrane. On the other hand, the disappearance of these QACs from rat jejunal loop also increased with the length of hydrocarbon chain over the range of 8.9 to 71.3%. A good correlation was found between binding to the brush-border membrane and disappearance from jejunal loop. From these results, it was suggested that the size of the hydrophobic part of a QAC molecule was a principal determinant of both absorption and membrane binding, and that the absorption of QACs with an appropriate sized hydrophobic part, was closely associated with the degree of binding to the membrane.

Pharmacokinetics and tissue distribution of the anticholinergics tiotropium and ipratropium in the rat and dog

“…The absorption in the two species is affected by gastrointestinal transit, luminal contents and membrane permeability, and one or several factors may cause the differences. In general, Saitoh [23] suggested that the size of the hydrophobic part of a quaternary ammonium compound was a principal determinant of both absorption and membrane binding. But the absorption process for quaternary ammonium ions is much more complicated.…”