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 treatment of ulcerative colitis and Crohn's disease of the large intestine, was investigated for its pharmacokinetic and toxicological properties, following local and systemic application. 5-ASA sulfate can be considered as a non-toxic agent after single oral intake in rats (14-day LD50 > 6000 mg/kg b.w.). Oral application of 2500 mg 5-ASA sulfate/kg b.w./d for 28 days to rats resulted in significantly increased body weight gain and food and water consumption. Alanine aminotransferase and alkaline phosphatase values were elevated in high-dosed (2500 mg/kg b.w./d p.o.) males. Relative liver weights were significantly increased in high-dosed males and females and the macroscopical inspection revealed thickened liver margins. The no-effect level following 28 days of oral application to rats was determined as 500 mg 5-ASA sulfate/kg b.w./d. In acute local tolerance studies in rabbits, 5-ASA sulfate is rated as non-irritant to the skin and the eye. After a single oral administration of 1800 mg 5-ASA sulfate to 5 healthy human 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 dose. A high faecal excretion of the active metabolite 5-aminosalicylic acid (5-ASA) (21.2% of the administered dose) and a low urinary excretion (1.4% of the administered dose) were observed.
Herzog
R
R
Henning Berlin GmbH, Germany.
Leuschner
J
J
D000636:Aminosalicylic Acids / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000633:toxicity*; D000818:Animals; D004435:Eating / Q000187:drug effects; D005123:Eye / Q000187:drug effects; D005243:Feces / Q000737:chemistry; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D007408:Intestinal Absorption; D007509:Irritants / Q000633:toxicity; D007928:Lethal Dose 50; D008297:Male; D019804:Mesalamine; D009929:Organ Size / Q000187:drug effects; D011817:Rabbits; D051381:Rats; D017208:Rats, Wistar; D012867:Skin / Q000187:drug effects; D015430:Weight Gain / Q000187:drug effects
D000636:Aminosalicylic Acids; D007509:Irritants; D019804:Mesalamine