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

• Published in: Clinical and molecular hepatology Vol. 20; no. 3; pp. 291 - 299
• Main Authors: Kim, Hyeyoung, Yi, Nam-Joon, Lee, Juyeun, Kim, Joohyun, Moon, Mi-Ra, Jeong, Jaehong, Lee, Jeong-Moo, You, Tae Suk, Suh, Suk-Won, Park, Min-Su, Choi, YoungRok, Hong, Geun, Lee, Hae Won, Lee, Kwang-Woong, Suh, Kyung-Suk
• Format: Journal Article
• Language: English
• Published: Korea (South) Korean Association for the Study of the Liver 01.09.2014; The Korean Association for the Study of the Liver; 대한간학회
• Subjects: Adult; Aged; Area Under Curve; Area under the curve; Biopsy; Blood; Creatinine; Drug dosages; Drug Therapy, Combination; Female; Follow-Up Studies; Gastrointestinal Diseases - etiology; Graft Rejection - prevention & control; Hepatitis B; Humans; Immunosuppressive Agents - blood; Immunosuppressive Agents - pharmacokinetics; Leukopenia - etiology; Liver - pathology; Liver cancer; Liver Failure - therapy; Liver transplant; Liver Transplantation; Liver transplants; Male; Middle Aged; Mycophenolate mofeti; Mycophenolic acid; Mycophenolic Acid - adverse effects; Mycophenolic Acid - analogs & derivatives; Mycophenolic Acid - blood; Mycophenolic Acid - pharmacokinetics; Original; Patients; Pharmacokinetics; Retrospective Studies; Review boards; ROC Curve; Tacrolimus - therapeutic use; Therapeutic drug monitoring; Tissue Donors; 내과학; Therapeutic drug monitoring; Liver transplant; Mycophenolate mofeti; Mycophenolic acid; Area under the curve
• ISSN: 2287-2728; 2287-285X; 2287-285X
• DOI: 10.3350/cmh.2014.20.3.291

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). 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. 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. 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.