Clin Mol Hepatol.  2014 Sep;20(3):291-299. 10.3350/cmh.2014.20.3.291.

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

• Kim H
• Yi NJ
• Lee J
• Kim J
• Moon MR
• Jeong J
• Lee JM
• You TS
• Suh SW
• Park MS
• Choi Y
• Hong G
• Lee HW
• Lee KW
• Suh KS

• KMID: 2069766
• DOI: http://doi.org/10.3350/cmh.2014.20.3.291

Abstract

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 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, 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.

Keyword

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

MeSH Terms

Adult
Aged
Area Under Curve
Drug Therapy, Combination
Female
Follow-Up Studies
Gastrointestinal Diseases/etiology
Graft Rejection/prevention & control
Humans
Immunosuppressive Agents/blood/*pharmacokinetics
Leukopenia/etiology
Liver/pathology
Liver Failure/*therapy
*Liver Transplantation
Male
Middle Aged
Mycophenolic Acid/adverse effects/*analogs & derivatives/blood/pharmacokinetics
ROC Curve
Retrospective Studies
Tacrolimus/therapeutic use
Tissue Donors
Immunosuppressive Agents
Mycophenolic Acid
Tacrolimus