title: Safety of reduced dose of mycophenolate mofetil combined with tacrolimus in living-donor liver transplantation.
abstract: OBJECTIVE
  The dose of mycophenolate mofetil (MMF) has been reduced in Asia due to side effects associated with the conventional fixed dose of 2-3 g/day. We aimed to determine the pharmacokinetics of a reduced dose of MMF and to validate its feasibility in combination with tacrolimus in living-donor liver transplantation (LDLT).
  
  
  METHODS
  Two sequential studies were performed in adult LDLT between October 2009 and 2011. First, we performed a prospective pharmacokinetic study in 15 recipients. We measured the area under the curve from 0 to 12 hours (AUC(0-12)) for mycophenolic acid at postoperative days 7 and 14, and we performed a protocol biopsy before discharge. Second, among 215 recipients, we reviewed 74 patients who were initially administered a reduced dose of MMF (1.0 g/day) with tacrolimus (trough, 8-12 ng/mL during the first month, and 5-8 ng/mL thereafter), with a 1-year follow-up. We performed protocol biopsies at 2 weeks and 1 year post-LDLT.
  
  
  RESULTS
  In the first part of study, AUC(0-12) was less than 30 mgh/L in 93.3% of cases. In the second, validating study, 41.9% of the recipients needed dose reduction or cessation due to side effects within the first year after LDLT. At 12 months post-LDLT, 17.6% of the recipients were administered a lower dose of MMF (0.5 g/day), and 16.2% needed permanent cessation due to side effects. The 1- and 12-month rejection-free survival rates were 98.6% and 97.3%, respectively.
  
  
  CONCLUSIONS
  A reduced dose of MMF was associated with low blood levels compared to the existing recommended therapeutic range. However, reducing the dose of MMF combined with a low level of tacrolimus was feasible clinically, with an excellent short-term outcome in LDLT.
authors.affiliation: Department of Surgery, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Hyeyoung
authors.initials: H
authors.lastname: Kim
authors.affiliation: Department of Surgery, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Nam-Joon
authors.initials: NJ
authors.lastname: Yi
authors.affiliation: Department of Pharmacy, Seoul National University Hospital, Seoul, Korea.
authors.forename: Juyeun
authors.initials: J
authors.lastname: Lee
authors.affiliation: Department of Surgery, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Joohyun
authors.initials: J
authors.lastname: Kim
authors.affiliation: Department of Pharmacy, Seoul National University Hospital, Seoul, Korea.
authors.forename: Mi-Ra
authors.initials: MR
authors.lastname: Moon
authors.affiliation: Department of Surgery, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Jaehong
authors.initials: J
authors.lastname: Jeong
authors.affiliation: Department of Surgery, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Jeong-Moo
authors.initials: JM
authors.lastname: Lee
authors.affiliation: Department of Surgery, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Tae Suk
authors.initials: TS
authors.lastname: You
authors.affiliation: Department of Surgery, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Suk-Won
authors.initials: SW
authors.lastname: Suh
authors.affiliation: Department of Surgery, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Min-Su
authors.initials: MS
authors.lastname: Park
authors.affiliation: Department of Surgery, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: YoungRok
authors.initials: Y
authors.lastname: Choi
authors.affiliation: Department of Surgery, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Geun
authors.initials: G
authors.lastname: Hong
authors.affiliation: Department of Surgery, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Hae Won
authors.initials: HW
authors.lastname: Lee
authors.affiliation: Department of Surgery, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Kwang-Woong
authors.initials: KW
authors.lastname: Lee
authors.affiliation: Department of Surgery, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Kyung-Suk
authors.initials: KS
authors.lastname: Suh
mesh_terms: D000328:Adult; D000368:Aged; D019540:Area Under Curve; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D005767:Gastrointestinal Diseases / Q000209:etiology; D006084:Graft Rejection / Q000517:prevention & control; D006801:Humans; D007166:Immunosuppressive Agents / Q000097:blood / Q000493:pharmacokinetics*; D007970:Leukopenia / Q000209:etiology; D008099:Liver / Q000473:pathology; D017093:Liver Failure / Q000628:therapy*; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics; D012372:ROC Curve; D012189:Retrospective Studies; D016559:Tacrolimus / Q000627:therapeutic use; D014019:Tissue Donors
chemical_list: D007166:Immunosuppressive Agents; D009173:Mycophenolic Acid; D016559:Tacrolimus
keywords: Area under the curve; Liver transplant; Mycophenolate mofeti; Mycophenolic acid; Therapeutic drug monitoring