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.
Berglindh
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T
Department of Biomedical Research, Pharmacia AB, Uppsala, Sweden.
Landström
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E
Bergqvist
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E
D000222:Adaptation, Physiological; D000636:Aminosalicylic Acids / Q000627:therapeutic use / Q000633:toxicity*; D000818:Animals; D003967:Diarrhea / Q000139:chemically induced*; D006801:Humans; D007408:Intestinal Absorption / Q000187:drug effects; D051381:Rats; D014882:Water-Electrolyte Balance / Q000187:drug effects*
D000636:Aminosalicylic Acids; C032587:olsalazine