Safety of reduced dose of mycophenolate mofetil combined with tacrolimus in living-donor liver transplantation.
10.3350/cmh.2014.20.3.291
- Author:
Hyeyoung KIM
1
;
Nam Joon YI
;
Juyeun LEE
;
Joohyun KIM
;
Mi Ra MOON
;
Jaehong JEONG
;
Jeong Moo LEE
;
Tae Suk YOU
;
Suk Won SUH
;
Min Su PARK
;
Youngrok CHOI
;
Geun HONG
;
Hae Won LEE
;
Kwang Woong LEE
;
Kyung Suk SUH
Author Information
1. Department of Surgery, Seoul National University College of Medicine, Seoul, Korea. gsleenj@hanmail.net
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords:
Area under the curve;
Mycophenolate mofeti;
Mycophenolic acid;
Therapeutic drug monitoring;
Liver transplant
- MeSH:
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
- From:Clinical and Molecular Hepatology
2014;20(3):291-299
- CountryRepublic of Korea
- Language:English
-
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.
