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( Hye Young Kim ),( Nam Joon Yi ),( Ju Yeun Lee ),( Joo Hyun Kim ),( Mi Ra Moon ),( Jae Hong Jeong ),( Jeong Moo Lee ),( Tae Suk You ),( Suk Won Suh ),( Min Su Park ),( Young Rok Choi ),( Ge Un Hong ) 대한간학회 2014 Clinical and Molecular Hepatology(대한간학회지) Vol.20 No.3
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 (AUC0-12) for mycophenolic acid at postoperative days 7 and 14, and we performeda 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, AUC0-12 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. (Clin Mol Hepatol 2014;20:291-299)