title: Therapeutic drug monitoring of enteric-coated mycophenolate sodium by limited sampling strategies is associated with a high rate of failure.
abstract: BACKGROUND
  Therapeutic drug monitoring of mycophenolic acid (MPA) is usually performed with a limited sampling strategy (LSS), which relies on a limited number of blood samples and subsequent extrapolation of the global exposure to MPA. LSS is usually performed successfully with mycophenolate mofetil (MMF), but data on enteric-coated mycophenolate sodium (EC-MPS) are scarce. Here, we evaluated the feasibility of 6-h LSS therapeutic drug monitoring with EC-MPS compared with MMF monitoring among kidney transplant recipients.
  
  
  METHODS
  Sixty-two patients who received EC-MPS during the first 6 months of transplantation were compared with a matched group of 64 MMF-treated kidney transplant recipients. The area under the curve (AUC) was computed by LSS using multiple concentration time points (0, 1, 2, 3 and 6 h post-dose) and a trapezoidal rule. Patients had MPA therapeutic drug monitoring performed on two occasions, one within 2 weeks and the second after 3-4 months of transplantation.
  
  
  RESULTS
  EC-MPS monitoring and MMF therapeutic drug monitoring were not interpretable in 34.5% (n = 40/116) and 1.8% (n = 2/112) of patients, respectively {relative risk [RR] 19.3 [95% confidence interval (CI) 4.8-78.0]; P < 0.0001}. The main cause of abnormal EC-MPS therapeutic drug monitoring was delayed absorption of both the previous evening and the morning dose, resulting in MPA plasma levels before the next morning dose being higher than MPA plasma levels measured at 1, 2 and 3 h after taking EC-MPS. Cyclosporin in association with MMF significantly increased the risk of low AUC values (<30 mg h/L) in comparison with tacrolimus [55% (n = 11/20) and 10% (n = 9/88), respectively; RR 5.4 (95% CI 2.6-11.2); P < 0.0001].
  
  
  CONCLUSIONS
  The risk of therapeutic drug monitoring failure with EC-MPS is >30% during the first 6 months of renal transplantation. Delayed pharmacokinetics was the main reason. In contrast, the risk of therapeutic drug monitoring failure was substantially lower with MMF.
authors.affiliation: Department of Nephrology , ULB Hôpital Erasme , Brussels , Belgium.
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Hougardy
authors.affiliation: Department of Nephrology , ULB Hôpital Erasme , Brussels , Belgium.
authors.forename: Laurette
authors.initials: L
authors.lastname: Maufort
authors.affiliation: Department of Clinical Chemistry , ULB Hôpital Erasme , Brussels , Belgium.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Cotton
authors.affiliation: Department of Nephrology , ULB Hôpital Erasme , Brussels , Belgium.
authors.forename: Julien
authors.initials: J
authors.lastname: Coussement
authors.affiliation: Department of Nephrology , ULB Hôpital Erasme , Brussels , Belgium.
authors.forename: Dimitri
authors.initials: D
authors.lastname: Mikhalski
authors.affiliation: Department of Nephrology , Universitair Ziekenhuis Brussel , Brussels , Belgium.
authors.forename: Karl M
authors.initials: KM
authors.lastname: Wissing
authors.affiliation: Department of Nephrology , ULB Hôpital Erasme , Brussels , Belgium.
authors.forename: Alain
authors.initials: A
authors.lastname: Le Moine
authors.affiliation: Department of Nephrology , ULB Hôpital Erasme , Brussels , Belgium.
authors.forename: Nilufer
authors.initials: N
authors.lastname: Broeders
authors.affiliation: Department of Nephrology , Universitair Ziekenhuis Antwerpen , Brussels , Belgium.
authors.forename: Daniel
authors.initials: D
authors.lastname: Abramowicz
keywords: enteric coating; kidney transplantation; mycophenolate mofetil; pharmacokinetics; suppression of area under curves