Induction of and adaptation to olsalazine induced intestinal volume load

Olsalazine is a new drug for the treatment of ulcerative and Crohn's colitis. The toxicological, pharmacological and pharmacokinetic profiles of olsalazine are excellent; the only side-effect noted from clinical trials with olsalazine is an increased incidence of loose stools and occasional diarrhoea. At high olsalazine concentrations, a direct effect on the net water absorption of the intestine is apparent. This effect is not due to a decrease in absorption, but to an induction of a rapidly reversible, Cl- dependent water secretion. In rats experimentally subjected to olsalazine induced diarrhoea (150 mg/kg), a total adaptation occurs within 3-4 days. This adaptation is not due to tachyphylaxis, but to an increased absorption capacity in the colon and caecum. Similar adaptation has been noted in other species including man.