Influence of 1,8-dihydroxyanthraquinone and loperamide on the paracellular permeability across colonic mucosa

Abstract

Administration of 1,8‐dihydroxyanthraquinone (DHA) markedly increases the permeability of guinea‐pig colonic mucosa. In 1 h 25% of the administered dose of99m Tc‐EDTA complex leaks through the mucosa. Orally administered loperamide blocks the99m Tc‐EDTA transfer after DHA administration. Loperamide injected in situ in the ligated colon segment shows the same blocking properties of the transfer rate of the complex. These findings suggest that the opposing action on fluid transport of the laxative DHA and the antidiarrhoeal loperamide could be due to these drugs affecting the permeability of the colonic mucosa. The minimal dose of loperamide, able to restore normal permeability, was as low as 0·01 mg kg−1.

Intestinal permeability: functional assessment and significance

“…Cytotoxic drugs, such as 5-fluorouracil [199] or methotrexate [200], and radiotherapy with regional hyperthermia [136] also appear to increase intestinal permeability, but it is not clear whether this has any effect on drug absorption or efficacy. The anti-diarrhoea1 agent loperamide inhibits the increase in permeation of EDTA caused by anthraquinone laxatives in perfused guinea-pig colon [201] and there has been interest in the possibility that bile acid adjuvants may enhance paracellular absorption of poorly absorbed drugs [202]. The detergent cetyltrimethyl-ammonium bromide (Cetrimide) also increases intestinal permeability to larger molecules such as lactulose and EDTA, but not to monosaccharides [42].…”

The Effect of Gallotannins and (+)-Catechin on the Stimulated Fluid Secretion on the Colon, Following a Rhein Perfusion in Guinea Pigs1

“…Their influence on gut motility, transit time, and motor activity has been described for opoids (1,2), indomethacm and aspirin (3), phiorizin (4), coichicin and vinblastin (5,6), ethanol (7), and loperamide (8). We studied the effect of antisecretory agents on fluid and electrolyte transport, and on paracellular permeability (9,10). Anyway, the exact mode of action of antisecretory drugs is not fully understood.…”