Safety of reduced dose of mycophenolate mofetil combined with tacrolimus in living-donor liver transplantation

Hyeyoung Kim, Nam Joon Yi, Juyeun Lee, Joohyun Kim, Mi Ra Moon, Jaehong Jeong, Jeong Moo Lee, Tae You, Suk Won Suh, Min Su Park, Young Rok Choi, Geun Hong, Hae W.on Lee, Kwang Woong Lee, Kyung Suk Suh

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7 Scopus citations


BACKGROUND/AIMS: 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.

Original languageEnglish
Pages (from-to)291-299
Number of pages9
JournalClinical and molecular hepatology
Issue number3
StatePublished - 1 Sep 2014


  • Area under the curve
  • Liver transplant
  • Mycophenolate mofeti
  • Mycophenolic acid
  • Therapeutic drug monitoring


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