Faculty Collaboration Database

Safety of reduced dose of mycophenolate mofetil combined with tacrolimus in living-donor liver transplantation. Clin Mol Hepatol 2014 Sep;20(3):291-9

Date

10/17/2014

Pubmed ID

25320733

Pubmed Central ID

PMC4197178

DOI

10.3350/cmh.2014.20.3.291

Scopus ID

2-s2.0-84932161774 (requires institutional sign-in at Scopus site)   7 Citations

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 (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.

Author List

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

Author

Joohyun Kim MD, PhD Associate Professor in the Surgery department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adult
Aged
Area Under Curve
Drug Therapy, Combination
Female
Follow-Up Studies
Gastrointestinal Diseases
Graft Rejection
Humans
Immunosuppressive Agents
Leukopenia
Liver
Liver Failure
Liver Transplantation
Male
Middle Aged
Mycophenolic Acid
ROC Curve
Retrospective Studies
Tacrolimus
Tissue Donors