Ascitic fluid modifying the distribution of sulphafurazole in rats with intestinal occlusion.

Abstract

In order to confirm our previous findings of increased sulphafurazole (sulfisoxazole, SF) inactivation by intestinal occlusion, SF was given intravenously 20 mg/kg to rats with a low small intestinal occlusion and to sham-operated controls 40-45 hours after the operation. Occlusion did not cause major changes in the distribution of SF to various tissues, but there were some indications of increased SF acetylation after occlusion. The occlusion rats produced ascitic fluid into the abdominal cavity and the total SF levels in the ascitic fluid were almost identical to those in blood, also after oral administration of SF, 50 mg/kg. After intraperitoneal administration of 2 ml of SF (60 microgram/ml) more SF accumulated into the small intestinal wall in occlusion rats than in controls, and the acetyl SF levels were increased in the small and large intestine. So, our previous suggestion of an increased excretory function of the large intestine in occlusion states may not be the only explanation for increased drug levels in the large intestine found after oral administration of SF. Part of the SF in the intestinal wall can also result from ascitic fluid SF, and ascites must be taken into account when considering drug pharmacokinetics.