A clinical assessment of mycophenolate drug monitoring after liver transplantation.
BACKGROUND
Recent findings have suggested the clinical utility of therapeutic drug monitoring (TDM) in patients treated with mycophenolate mofetil (MMF).


OBJECTIVE
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 < or = 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 microg/mL. Correlation between MMF dosage and MPA concentration showed wide interindividual variations (n = 304, r(2) = 0.271, p < 0.001), in which r(2) 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, r(2) < 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 > or =1.0 microg/mL in 87% and >2.0 microg/mL in 56.5%.


CONCLUSIONS
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.
Hwang
Shin
S
Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
Lee
Sung-Gyu
SG
Ahn
Chul-Soo
CS
Kim
Ki-Hun
KH
Moon
Deok-Bog
DB
Ha
Tae-Yong
TY
Song
Gi-Won
GW
Jung
Dong-Hwan
DH
Choi
Nam-Kyu
NK
Kim
Kwan-Woo
KW
Yu
Young-Dong
YD
Park
Gil-Chun
GC
Park
Pyoung-Jae
PJ
Choi
Young-Il
YI
D000328:Adult; D016903:Drug Monitoring; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D011184:Postoperative Period; D016559:Tacrolimus / Q000627:therapeutic use
D007166:Immunosuppressive Agents; D009173:Mycophenolic Acid; D016559:Tacrolimus