title: Cyclosporine A-based immunotherapy in adult living donor liver transplantation: accurate and improved therapeutic drug monitoring by 4-hr intravenous infusion.
abstract: BACKGROUND
  A paucity of data exists for evaluating therapeutic drug monitoring in association with clinical outcomes of cyclosporine A (CYA) treatment in living donor liver transplantation (LDLT).
  
  
  METHODS
  A retrospective cohort analysis was conducted on 50 consecutive adult patients who underwent LDLT between 2001 and 2009 to investigate the feasibility and efficacy of 4-hr continuous intravenous infusion of CYA-based immunotherapy (4-hr CYA-IV, n=27) and compare the pharmacokinetic profile and short-term prognoses with an oral microemulsion formulation of CYA (CYA-ME, n=23).
  
  
  RESULTS
  All patients in the 4-hr CYA-IV group reached target CYA peak by day 3 compared with only 22% in the CYA-ME group (P<0.001). Adjustability to achieve the target range was easier in the 4-hr CYA-IV group compared with the CYA-ME group (P=0.017). Acute cellular rejection rate was lower in the 4-hr CYA-IV group (0%) compared with the CYA-ME group (17%, P=0.038). A subset analysis of the CYA-ME group revealed that CYA exposure was affected by external bile output (P=0.006). Patients in the CYA-ME group showed increased risk of switch to tacrolimus (35%) compared with the 4-hr CYA-IV group (7%, P=0.030). Toxicities and mortality rates were equivalent. The optimal initial dose of oral CYA at conversion from the 4-hr CYA-IV was considered to be 3-fold greater than that of the intravenous dose.
  
  
  CONCLUSIONS
  In LDLT, our 4-hr CYA-IV immunosuppression protocol was superior to CYA-ME oral dosing and allowed accurate therapeutic drug monitoring with excellent patient compliance.
authors.affiliation: Department of Surgery, Keio University School of Medicine, Shinjuku-ku, Tokyo, Japan.
authors.forename: Taizo
authors.initials: T
authors.lastname: Hibi
authors.forename: Minoru
authors.initials: M
authors.lastname: Tanabe
authors.forename: Ken
authors.initials: K
authors.lastname: Hoshino
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Fuchimoto
authors.forename: Shigeyuki
authors.initials: S
authors.lastname: Kawachi
authors.forename: Osamu
authors.initials: O
authors.lastname: Itano
authors.forename: Hideaki
authors.initials: H
authors.lastname: Obara
authors.forename: Masahiro
authors.initials: M
authors.lastname: Shinoda
authors.forename: Naoki
authors.initials: N
authors.lastname: Shimojima
authors.forename: Kentaro
authors.initials: K
authors.lastname: Matsubara
authors.forename: Yasuhide
authors.initials: Y
authors.lastname: Morikawa
authors.forename: Yuko
authors.initials: Y
authors.lastname: Kitagawa
mesh_terms: D000328:Adult; D015331:Cohort Studies; D016572:Cyclosporine / Q000008:administration & dosage* / Q000493:pharmacokinetics; D016903:Drug Monitoring; D004655:Emulsions; D005260:Female; D006084:Graft Rejection / Q000517:prevention & control; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D007262:Infusions, Intravenous; D016031:Liver Transplantation / Q000276:immunology; D019520:Living Donors; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012189:Retrospective Studies; D016896:Treatment Outcome
chemical_list: D004655:Emulsions; D007166:Immunosuppressive Agents; D016572:Cyclosporine