Non-antibiotic anti-diarrhoeal drugs: factors affecting oral bioavailability of berberine and loperamide in intestinal tissue

This review examines the anti-diarrhoeal actions of loperamide and berberine and shows evidence that there is much in common between the two agents in terms of their pharmacokinetics, an anti-motility action on intestinal smooth muscle and an anti-secretory effect on intestinal epithelia. Novel combined in vitro flux and short-circuit current data is presented illustrating that in normal rat intestinal epithelial tissue both agents require access to the basolateral side of the intestinal epithelium in order to inhibit effect on stimulated electrogenic chloride secretion, an effect most likely mediated by interaction with a potassium channel. Permeation and associated anti-secretory activity of luminally-applied berberine and loperamide, although normally poor, was permitted by the tight junction opener, cytochalasin D. There is a possibility that increased epithelial cell permeability, resulting from the loss of cell integrity occurring in conditions of secretory diarrhoea, can contribute to luminal effectiveness of anti-secretory/anti-motility agents.