Safety of reduced dose of mycophenolate mofetil combined with tacrolimus in living-donor liver transplantation
Korean Journal of Hepatology 2014³â 20±Ç 3È£ p.291 ~ p.299
±èÇý¿µ(Kim Hye-Young) - Seoul National University College of Medicine Department of Surgery
À̳²ÁØ(Yi Nam-Joon) - Seoul National University College of Medicine Department of Surgery
ÀÌÁÖ¿¬(Lee Ju-Yeun) - Seoul National University Hospital Department of Pharmacy
±èÁÖÇö(Kim Joo-Hyun) - Seoul National University College of Medicine Department of Surgery
¹®¹Ì¶ó(Moon Mi-Ra) - Seoul National University Hospital Department of Pharmacy
Á¤ÀçÈ«(Jeong Jae-Hong) - Seoul National University College of Medicine Department of Surgery
ÀÌÁ¤¹«(Lee Jeong-Moo) - Seoul National University College of Medicine Department of Surgery
À¯Å¼®(You Tae-Suk) - Seoul National University College of Medicine Department of Surgery
¼¼®¿ø(Suh Suk-Won) - Seoul National University College of Medicine Department of Surgery
¹Ú¹Î¼ö(Park Min-Su) - Seoul National University College of Medicine Department of Surgery
ÃÖ¿µ·Ï(Choi Young-Rok) - Seoul National University College of Medicine Department of Surgery
(Hong Geun) - Seoul National University College of Medicine Department of Surgery
ÀÌÇØ¿ø(Lee Hae-Won) - Seoul National University College of Medicine Department of Surgery
À̱¤¿õ(Lee Kwang-Woong) - Seoul National University College of Medicine Department of Surgery
¼°æ¼®(Suh Kyung-Suk) - Seoul National University College of Medicine Department of Surgery
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.
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Area under the curve, Mycophenolate mofeti, Mycophenolic acid, Therapeutic drug monitoring, Liver transplant
KMID :
1103920140200030291
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