title: Dexamethasone 21-sulfate improves the therapeutic properties of dexamethasone against experimental rat colitis by specifically delivering the steroid to the large intestine.
abstract: OBJECTIVE
  We investigated in vivo-colon targetability and therapeutic properties of DS against experimental rat colitis.
  
  
  METHODS
  The systemic absorption and colonic delivery of D after oral administration of DS was analyzed by examining the concentration of drugs in the GI tract, plasma, urine and feces. Therapeutic activity of DS was determined using a TNBS-induced rat colitis model. Adrenal suppression by DS administration was evaluated by monitoring the concentration of ACTH and corticosterone in the plasma.
  
  
  RESULTS
  DS administered orally was delivered efficiently to the large intestine resulting in D accumulation at the target site. In addition, DS was not detectable in the plasma and was detected very low in the urine after DS administration. The fecal and urinary recovery of D (after DS administration) was much greater and less than that after D administration, suggesting that DS should exhibit enhanced therapeutic activity and reduced systemic side effects. Consistent with this notion, DS was more effective than D in healing rat colitis. Moreover, oral administration of either D or DS reduced the plasma corticosterone and ACTH levels from the normal levels, which is significantly greater for D.
  
  
  CONCLUSIONS
  DS is a promising colon specific prodrug that improves therapeutic properties of D.
authors.affiliation: Laboratory of Biomedicinal/Medicinal Chemistry, College of Pharmacy, Pusan National University, Pusan, 609-735, Republic of Korea.
authors.forename: Inho
authors.initials: I
authors.lastname: Kim
authors.forename: Hyesik
authors.initials: H
authors.lastname: Kong
authors.forename: Younghyun
authors.initials: Y
authors.lastname: Lee
authors.forename: Sungchae
authors.initials: S
authors.lastname: Hong
authors.forename: Jungoh
authors.initials: J
authors.lastname: Han
authors.forename: Sunhwa
authors.initials: S
authors.lastname: Jung
authors.forename: Yunjin
authors.initials: Y
authors.lastname: Jung
authors.forename: Young Mi
authors.initials: YM
authors.lastname: Kim
mesh_terms: D000284:Administration, Oral; D000311:Adrenal Glands / Q000187:drug effects / Q000378:metabolism; D000324:Adrenocorticotropic Hormone / Q000097:blood; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D003092:Colitis / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D003106:Colon / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D003907:Dexamethasone / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000493:pharmacokinetics / Q000494:pharmacology*; D004195:Disease Models, Animal; D005243:Feces / Q000737:chemistry; D005765:Gastrointestinal Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D006854:Hydrocortisone / Q000097:blood; D007408:Intestinal Absorption; D008297:Male; D011355:Prodrugs / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013431:Sulfates / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D014302:Trinitrobenzenesulfonic Acid
chemical_list: D000893:Anti-Inflammatory Agents; D005765:Gastrointestinal Agents; D011355:Prodrugs; D013431:Sulfates; D003907:Dexamethasone; D014302:Trinitrobenzenesulfonic Acid; D000324:Adrenocorticotropic Hormone; D006854:Hydrocortisone