title: A clinical assessment of mycophenolate drug monitoring after liver transplantation.
abstract: 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.
authors.affiliation: Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Shin
authors.initials: S
authors.lastname: Hwang
authors.forename: Sung-Gyu
authors.initials: SG
authors.lastname: Lee
authors.forename: Chul-Soo
authors.initials: CS
authors.lastname: Ahn
authors.forename: Ki-Hun
authors.initials: KH
authors.lastname: Kim
authors.forename: Deok-Bog
authors.initials: DB
authors.lastname: Moon
authors.forename: Tae-Yong
authors.initials: TY
authors.lastname: Ha
authors.forename: Gi-Won
authors.initials: GW
authors.lastname: Song
authors.forename: Dong-Hwan
authors.initials: DH
authors.lastname: Jung
authors.forename: Nam-Kyu
authors.initials: NK
authors.lastname: Choi
authors.forename: Kwan-Woo
authors.initials: KW
authors.lastname: Kim
authors.forename: Young-Dong
authors.initials: YD
authors.lastname: Yu
authors.forename: Gil-Chun
authors.initials: GC
authors.lastname: Park
authors.forename: Pyoung-Jae
authors.initials: PJ
authors.lastname: Park
authors.forename: Young-Il
authors.initials: YI
authors.lastname: Choi
mesh_terms: 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
chemical_list: D007166:Immunosuppressive Agents; D009173:Mycophenolic Acid; D016559:Tacrolimus