title: Tacrolimus and mycophenolate mofetil provide effective immunosuppression in rat laryngeal transplantation.
abstract: OBJECTIVE
  Tacrolimus is efficacious in several transplantation settings. Some studies have demonstrated improved results using combination therapy with mycophenolate mofetil. Our primary objective was to evaluate the efficacy and optimal dosing of tacrolimus in preventing rejection, using an established rat model of laryngeal transplantation. Further, the ability of mycophenolate to allow lower dosing of tacrolimus while achieving equivalent immunosuppression was investigated.
  
  
  METHODS
  A dosage efficacy study with 10 experimental arms was conducted.
  
  
  METHODS
  Dosage groups were 0.1, 0.2, 0.3, and 0.6 mg/kg tacrolimus alone and 0.1 mg/kg tacrolimus combined with 15 mg/kg mycophenolate mofetil, 0.1 mg/kg tacrolimus combined with 30 mg/kg mycophenolate mofetil, 0.1 mg/kg tacrolimus combined with 40 mg/kg mycophenolate mofetil, 0.2 mg/kg tacrolimus combined with 15 mg/kg mycophenolate mofetil, 0.2 mg/kg tacrolimus combined with 30 mg/kg mycophenolate mofetil (30 d only), and 0.2 mg/kg tacrolimus combined with 40 mg/kg mycophenolate mofetil. Each group contained 8 to 10 rats. Grafts were harvested for histopathological analysis on day 15 or 30 after transplantation. Histopathological appearance of the graft was blindly graded according to an established scale. Dosage groups were compared on rejection score using Wilcoxon's rank sum test and the Jonckheere-Terpstra test for trend.
  
  
  RESULTS
  There was a significant association between increasing dose of tacrolimus and decreasing rejection score at both 15 and 30 days (P <.001). In the groups treated with 0.1 mg/kg T, an increasing dose of mycophenolate was associated with lower rejection scores at both 15 and 30 days (P =.001). In the group treated with 0.2 mg/kg T, there was no evidence that the addition of mycophenolate resulted in lower rejection at 15 days. However, at 30 days, combination therapy with increasing doses of mycophenolate was associated with decreasing rejection score (P =.002).
  
  
  CONCLUSIONS
  Tacrolimus is an effective immunosuppressive agent for laryngeal transplantation. Mycophenolate mofetil allows lower doses of tacrolimus to be used while preserving graft viability in the early post-transplantation period.
authors.affiliation: Department of Otolarynology and Communicative Disorders, The Cleveland Clinic Foundation, Ohio, 44195, USA. nelsonm1@ccf.org
authors.forename: Marc
authors.initials: M
authors.lastname: Nelson
authors.forename: Michael
authors.initials: M
authors.lastname: Fritz
authors.forename: Olivia
authors.initials: O
authors.lastname: Dan
authors.forename: Sarah
authors.initials: S
authors.lastname: Worley
authors.forename: Marshall
authors.initials: M
authors.lastname: Strome
mesh_terms: D000818:Animals; D004305:Dose-Response Relationship, Drug; D004306:Dose-Response Relationship, Immunologic; D006084:Graft Rejection / Q000473:pathology / Q000517:prevention & control; D007165:Immunosuppression Therapy; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D007830:Larynx / Q000473:pathology / Q000637:transplantation*; D008297:Male; D009173:Mycophenolic Acid / Q000008:administration & dosage* / Q000031:analogs & derivatives; D051381:Rats; D011917:Rats, Inbred Lew; D011919:Rats, Inbred Strains; D016559:Tacrolimus / Q000008:administration & dosage*
chemical_list: D007166:Immunosuppressive Agents; D009173:Mycophenolic Acid; D016559:Tacrolimus