Evaluation of 5-aminosalicyltaurine as a colon-specific prodrug of 5-aminosalicylic acid for treatment of experimental colitis.
We previously reported that 5-aminosalicyltaurine (taurine-conjugated 5-ASA, 5-ASA-Tau) showed a potential as a colon-specific prodrug of 5-aminosalicylic acid (5-ASA) by in vitro evaluation. In this report, we in vivo-evaluated 5-ASA-Tau as a colon-specific prodrug for treatment of experimental colitis. Taurine conjugation of 5-ASA greatly reduced absorption of 5-ASA from the intestine. Oral administration of taurine-conjugated 5-ASA not only increased the colonic delivery efficiency of 5-ASA but also decreased the systemic absorption of free 5-ASA as compared with that of 5-ASA and, moreover, taurine is similarly effective to known colon-specific carriers for 5-ASA, glycine and aspartic acid, suggesting that taurine conjugation is an efficient way to increase the therapeutic effect and to reduce the adverse effects of 5-ASA. Intracolonic treatment with combined 5-ASA/taurine additively ameliorated TNBS-induced colitis rats indicating that taurine acted as not only a promoiety but also a therapeutically active agent. Furthermore, 5-ASA-Tau is slightly more effective than sulfasalazine in alleviating the colonic inflammation induced by TNBS. Taken together, our data suggest that 5-ASA-Tau is a potential colon-specific prodrug of 5-aminosalicylic acid with improved therapeutic activity against inflammatory bowel disease.
Jung
Yunjin
Y
Lab of Biomedicinal Chemistry, College of Pharmacy, Pusan National University, Busan 609-735, Republic of Korea.
Kim
Hak-Hyun
HH
Kim
Heejung
H
Kong
Hyesik
H
Choi
Boim
B
Yang
Youngwook
Y
Kim
Youngmi
Y
D000636:Aminosalicylic Acids / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002851:Chromatography, High Pressure Liquid; D003092:Colitis / Q000139:chemically induced / Q000188:drug therapy*; D003106:Colon / Q000187:drug effects; D016503:Drug Delivery Systems; D005243:Feces / Q000737:chemistry; D005765:Gastrointestinal Agents / Q000627:therapeutic use; D007408:Intestinal Absorption; D008297:Male; D019804:Mesalamine / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use*; D011355:Prodrugs / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012460:Sulfasalazine / Q000627:therapeutic use; D013654:Taurine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use; D014302:Trinitrobenzenesulfonic Acid
C479530:5-aminosalicyltaurine; D000636:Aminosalicylic Acids; D000894:Anti-Inflammatory Agents, Non-Steroidal; D005765:Gastrointestinal Agents; D011355:Prodrugs; D013654:Taurine; D012460:Sulfasalazine; D019804:Mesalamine; D014302:Trinitrobenzenesulfonic Acid