EXPERIMENTAL STUDIES ON THE PHARMACOKINETICS AND TOXICITY OF 5-AMINOSALICYLIC ACID-O-SULFATE FOLLOWING LOCAL AND SYSTEMIC APPLICATION

5-Aminosalicylic acid-O-sulfate (5-ASA sulfate), a new agent for the t reatment of ulcerative colitis and Crohn's disease of the large intest ine, was investigated for its pharmacokinetic and toxicological proper ties, following local and systemic application. 5-ASA sulfate can be c onsidered as non-toxic agent after single oral intake in rat (14-day L D(50) > 6000 mg/kg b.w.). Oval application of 2500 mg 5-ASA sulfate/kg b.w./d for 28 days to rats resulted in significantly increased body w eight gain and food and water consumption. Alanine aminotransferase an d alkaline values were evaluated in high-dosed (2500 mg/kg b.w./d p.o. ) males. Relative liver weights were significantly increased in high-d osed males and females and the macroscopical inspection revealed thick ened liver margins. The no-effect level following 28 days of oral appl ications to rats was determined as 500 mg 5-ASA sulfate/kg b.w./d. In acute local tolerance studies in rabbits, 5-ASA sulfate to 5 healthy h uman test subjects, 5-ASA sulfate was almost completely metabolized by all test subjects within 3 days; mean urinary and faecal excretion of unchanged 5-ASA sulfate amounted to only 6.7% of the administered dos e. A high faecal excretion of the active metabolite 5-aminosalicylic a cid (5-ASA) (21.2% of the administered dose) and a low urinary excreti on (1.4% of the administered dose) were observed.