title: Glycyrrhizin enhances therapeutic activity of a colon-specific methylprednisolone prodrug against experimental colitis.
abstract: BACKGROUND
  Co-administration of a reduction inhibitor and a colon-specific prodrug of a glucocorticoid susceptible to colonic reductive metabolism is suggested as a strategy to circumvent the therapeutic loss of the glucocorticoid delivered to and acting locally at the large intestine.
  
  
  OBJECTIVE
  We examined whether the strategy was feasible as a pharmacotherapy for treatment of inflammatory bowel disease.
  
  
  METHODS
  Glycyrrhizin (GCZ), a reduction inhibitor, was tested for its inhibition of the colonic metabolism of methylprednisolone (MP). Therapeutic activity against TNBS-induced rat colitis and adrenal suppression were compared after oral administration of methylprednisolone 21-sulfate sodium (MPS), a colon-specific prodrug of MP, or MPS/GCZ to colitic rats.
  
  
  RESULTS
  Upon incubation of MP with the cecal contents, MP disappeared, and this was delayed by addition of GCZ. In addition, more MP produced from MPS in the cecal contents accumulated in the presence of GCZ. Consistent with these results, upon oral administration of MPS/GCZ, MPS or MP, MP was detected at a greater level in the large intestine for MPS/GCZ. MPS/GCZ ameliorated TNBS-induced colitis of rats, and this therapeutic effect was superior to that of MPS and MP. Moreover, MPS/GCZ decreased the plasma levels of corticosterone and ACTH to a greater extent than MPS, but less than MP.
  
  
  CONCLUSIONS
  Co-administration of GCZ, a reduction inhibitor, may be a plausible strategy to reduce the therapeutic loss of MP produced from MPS in the large intestine, thus improving the therapeutic property of the prodrug against inflammatory bowel disease.
authors.affiliation: College of Pharmacy, Pusan National University, Busan, 609-735, South Korea.
authors.forename: Yonghyun
authors.initials: Y
authors.lastname: Lee
authors.forename: Seongkeun
authors.initials: S
authors.lastname: Jeong
authors.forename: Wooseong
authors.initials: W
authors.lastname: Kim
authors.forename: Hyunjeong
authors.initials: H
authors.lastname: Kim
authors.forename: Jeong-Hyun
authors.initials: JH
authors.lastname: Yoon
authors.forename: Seong Hoon
authors.initials: SH
authors.lastname: Jeong
authors.forename: Yunjin
authors.initials: Y
authors.lastname: Jung
mesh_terms: D000311:Adrenal Glands / Q000187:drug effects; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000378:metabolism / Q000627:therapeutic use*; D003092:Colitis / Q000188:drug therapy* / Q000378:metabolism; D004353:Drug Evaluation, Preclinical; D004357:Drug Synergism; D019695:Glycyrrhizic Acid / Q000627:therapeutic use*; D008297:Male; D008775:Methylprednisolone / Q000378:metabolism / Q000627:therapeutic use*; D011355:Prodrugs / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000893:Anti-Inflammatory Agents; D011355:Prodrugs; D019695:Glycyrrhizic Acid; D008775:Methylprednisolone