Synthesis and properties of N,N'-bis(5-aminosalicyl)-L-cystine as a colon-specific deliverer of 5-aminosalicylic acid and cystine.
N,N(')-bis(5-aminosalicyl)-L-cystine (5-ASA-Cys) was prepared by a simple synthetic route. 5-ASA-Cys was not degraded in pH 1.2 and 6.8 buffer solutions, and in the homogenates of the upper intestine. In marked contrast, 5-ASA-Cys was deconjugated extensively to liberate 5-ASA in the cecal contents. Upon oral administration of 5-ASA-Cys to rats, the plasma concentration of 5-ASA-Cys was extremely low and the urinary recovery of 5-ASA-Cys was approximately 10% of the dose. These results suggest that 5-ASA-Cys administered orally is delivered efficiently to the large intestine followed by deconjugation to liberate 5-ASA and cystine.
Kim
Heejung
H
Laboratory of Biomedicinal, College of Pharmacy, Pusan National University, Busan, Korea.
Kim
Duksoo
D
Choi
Daekyu
D
Jeon
Hyunchu
H
Han
Jungoh
J
Jung
Yunjin
Y
Kong
Hyesik
H
Kim
Young Mi
YM
D000284:Administration, Oral; D000636:Aminosalicylic Acids / Q000008:administration & dosage / Q000138:chemical synthesis / Q000493:pharmacokinetics*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000138:chemical synthesis / Q000493:pharmacokinetics*; D001711:Biotransformation; D002432:Cecum / Q000378:metabolism; D003106:Colon / Q000378:metabolism*; D003553:Cystine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000493:pharmacokinetics; D004355:Drug Stability; D005753:Gastric Mucosa / Q000378:metabolism; D005765:Gastrointestinal Agents / Q000008:administration & dosage / Q000138:chemical synthesis / Q000493:pharmacokinetics*; D006626:Hippurates / Q000493:pharmacokinetics; D006863:Hydrogen-Ion Concentration; D007408:Intestinal Absorption; D007421:Intestine, Small / Q000378:metabolism; D008297:Male; D011355:Prodrugs / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
C116885:5-aminosalicyl-glycine; D000636:Aminosalicylic Acids; D000893:Anti-Inflammatory Agents; D005765:Gastrointestinal Agents; D006626:Hippurates; C528877:N,N'-bis(5-aminosalicyl)cystine; D011355:Prodrugs; D003553:Cystine