A clinical assessment of mycophenolate drug monitoring after liver transplantation

Abstract

Recent findings have suggested the clinical utility of therapeutic drug monitoring (TDM) in patients treated with mycophenolate mofetil (MMF). To assess whether routine mycophenolic acid (MPA) TDM is beneficial and how to utilize it. A series of short-term prospective studies on TDM for MPA and/or tacrolimus was performed at a large-volume center. 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%. 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.