A clinical assessment of mycophenolate drug monitoring after liver transplantation

作者：Hwang Shin; Lee Sung Gyu^*; Ahn Chul Soo; Kim Ki Hun; Moon Deok Bog; Ha Tae Yong; Song Gi Won; Jung Dong Hwan; Choi Nam Kyu; Kim Kwan Woo; Yu Young Dong; Park Gil Chun; Park Pyoung Jae; Choi Young Il

来源：Clinical Transplantation, 2010, 24(2): E35-E42.

DOI：10.1111/j.1399-0012.2009.01166.x

• immunosuppression
• liver transplantation
• mycophenolate mofetil
• mycophenolic acid
• therapeutic drug monitoring

Background:
Recent findings have suggested the clinical utility of therapeutic drug monitoring (TDM) in patients treated with mycophenolate mofetil (MMF).
Aim:
To assess whether routine mycophenolic acid (MPA) TDM is beneficial and how to utilize it.
Methods:
A series of short-term prospective studies on TDM for MPA and/or tacrolimus was performed at a large-volume center.
Results:
The 673 adult liver transplants were divided into four groups based on immunosuppressive regimens as tacrolimus monotherapy (n = 369), tacrolimus-MMF therapy (n = 270), MMF-minimal tacrolimus therapy (n = 17), and MMF monotherapy (n = 17). There was a significant difference of tacrolimus concentration between the groups receiving tacrolimus monotherapy and tacrolimus-MMF therapy during the first two yr (at two yr: 8.4 +/- 2.7 vs. 6.3 +/- 2.6 ng/mL; p < 0.002). MMF-minimal tacrolimus therapy and MMF monotherapy were applied after first three months and MPA levels ranged from 1.8 to 5.3 mu g/mL. Correlation between MMF dosage and MPA concentration showed wide interindividual variations (n = 304, r2 = 0.271, p < 0.001), in which r2 was fluctuating from 0.056 to 0.213 according to the post-transplant period over five yr; wide intraindividual variation was also observed during the first two months (n = 12, r2 < 0.2, p > 0.195). About 10% of patients were classified as poor MMF absorber and excluded from MMF usage. Mean MPA level leading to successful MMF monotherapy or MMF-minimal tacrolimus therapy was >= 1.0 mu g/mL in 87% and > 2.0 mu g/mL in 56.5%.
Conclusion:
MPA TDM-based MMF dosage adjustment enabled us to administer MMF more confidently than categorical dosing. MPA TDM appears to be a useful tool to cope with the wide pharmacokinetic variability of MMF after liver transplantation.

• 出版日期2010-4