Therapeutic drug monitoring of mycophenolic acid: does it improve patient outcome?
Treatment with the immunosuppressive agent mycophenolate mofetil (MMF) decreases the risk of rejection after renal transplantation and improves graft survival compared with azathioprine. The exposure to the active metabolite mycophenolic acid (MPA) is correlated to the risk of developing acute rejection. The interpatient variability in exposure of MPA is wide relative to the proposed therapeutic window of the MPA AUC(0 12) (30 - 60 mg.h/l). The pharmacokinetics of MPA are influenced by patient characteristics such as gender, time after transplantation, serum albumin concentration, renal function, comedication and pharmacogenetic factors. Therapeutic drug monitoring is likely to reduce inter-patient variability. Limited sampling strategies are used to predict the full AUC(0 12). Three prospective randomised studies compared concentration controlled MMF therapy to a fixed-dose regimen. Preliminary outcomes of these studies showed conflicting results and longer follow up is needed to further clarify the role of therapeutic drug monitoring in increasing the therapeutic potential of MMF.
de Winter
Brenda C M
BC
Erasmus Medical Center, Department of Hospital Pharmacy, Clinical Pharmacology Unit, Rotterdam, The Netherlands. b.dewinter@erasmusmc.nl
Mathôt
Ron A A
RA
van Hest
Reinier M
RM
van Gelder
Teun
T
D000903:Antibiotics, Antineoplastic / Q000493:pharmacokinetics / Q000627:therapeutic use; D019540:Area Under Curve; D016903:Drug Monitoring / Q000379:methods*; D006084:Graft Rejection / Q000517:prevention & control*; D006801:Humans; D016030:Kidney Transplantation; D009173:Mycophenolic Acid / Q000493:pharmacokinetics / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D012307:Risk Factors; D016896:Treatment Outcome
D000903:Antibiotics, Antineoplastic; D009173:Mycophenolic Acid