N,N'-Bis(5-aminosalicyl)-L-cystine is a potential colon-specific 5-aminosalicylic acid prodrug with dual therapeutic effects in experimental colitis.

Abstract

To evaluate N,N'-bis(5-aminosalicyl)-L-cystine (5-ASA-Cys) as a potential colon-specific 5-aminosalicylic acid prodrug with dual therapeutic effects in experimental colitis, the pharmacokinetics and therapeutic activity were investigated after oral administration of 5-ASA-Cys and amelioration of experimental colitis was compared after rectal administration of 5-aminosalicylic acid (5-ASA) and/or cysteine. In addition, the gluthathione (GSH) level in the inflamed colonic tissue was examined after administration of cysteine or 5-ASA-Cys. Oral administration of 5-ASA-Cys delivered much greater amount of 5-ASA to the large intestine and excreted lower amount of 5-ASA via urine than that of free 5-ASA. Oral administration of 5-ASA-Cys ameliorated experimental colitis of rats induced by TNBS, which was more effective than that of sulfasalazine. Although cysteine administered rectally was not significantly effective, intracolonic treatment with both 5-ASA and cysteine showed a synergic effect in alleviating the rat colitis. Furthermore, not only 5-ASA-Cys administered orally but also cysteine administered rectally increased the glutathione level in the inflamed colonic tissue. Taken together, these results suggest that 5-ASA-Cys is a potential colon specific 5-ASA prodrug with dual therapeutic effects on experimental colitis and cysteine modulation of the glutathione level may be relevant to the dual effects of the prodrug.

• Authors: Heejung Kim, Jeongsoon Huh, Hyunchu Jeon, Daekyu Choi, Jungoh Han, Youngmi Kim, Yunjin Jung
• Journal: Journal of pharmaceutical sciences (J Pharm Sci) Vol. 98 Issue 1 Pg. 159-68 (Jan 2009) ISSN: 1520-6017 [Electronic] United States
• PMID: 18399548 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: (c) 2008 Wiley-Liss, Inc. and the American Pharmacists Association

Chemical References

• Aminosalicylic Acids
• N,N'-bis(5-aminosalicyl)cystine
• Prodrugs
• Cystine

Topics

• Aminosalicylic Acids (administration & dosage, chemistry)
• Animals
• Colitis (drug therapy, metabolism)
• Colon (drug effects, metabolism)
• Cystine (administration & dosage, analogs & derivatives, chemistry)
• Male
• Prodrugs (administration & dosage, chemistry)
• Rats
• Rats, Sprague-Dawley