title: Mycophenolate pharmacokinetics and inosine monophosphate dehydrogenase activity in liver transplant recipients with an emphasis on therapeutic drug monitoring.
abstract: BACKGROUND
  The pharmacokinetics of the immunosuppressant mycophenolic acid (MPA) demonstrates high inter- and intra-patient variability. Variation in the binding of MPA to albumin has been postulated to be an important factor in this variability, and monitoring of free MPA has been suggested to improve therapeutic drug monitoring (TDM) of MPA. Inosine monophosphate dehydrogenase (IMPDH) is the target enzyme for MPA, therefore the IMPDH activity in lymphocytes can serve as a marker of the MPA-specific response. This study aimed to explore how the albumin concentration influences the free concentration of MPA in liver transplant recipients and to assess whether alteration in the free MPA influences IMPDH activity in CD4 + cells.
  
  
  METHODS
  Blood samples were taken from 20 liver transplant recipients on two separate occasions (days 3-5 and 16-21). Total and free concentrations of MPA, and IMPDH activity were measured during the first 4 h of each dose interval.
  
  
  RESULTS
  Albumin levels correlated with the free fraction of MPA. However, the total MPA and free MPA were equal predictors of the immunosuppressive response as defined by IMPDH activity.
  
  
  CONCLUSIONS
  Total and free MPA are equally good predictors of the immunosuppressive effect exerted by MPA as defined by IMPDH activity. IMPDH activity measurements represent a promising approach to TDM in patients treated with MPA.
authors.affiliation: Department of Anaesthesiology, Oslo University Hospital, Oslo, Norway. palre@ous-hf.no
authors.forename: Pål A
authors.initials: PA
authors.lastname: Reine
authors.forename: Nils T
authors.initials: NT
authors.lastname: Vethe
authors.forename: Ulf E
authors.initials: UE
authors.lastname: Kongsgaard
authors.forename: Anders M
authors.initials: AM
authors.lastname: Andersen
authors.forename: Pål D
authors.initials: PD
authors.lastname: Line
authors.forename: Ali M
authors.initials: AM
authors.lastname: Ali
authors.forename: Stein
authors.initials: S
authors.lastname: Bergan
mesh_terms: D000328:Adult; D000368:Aged; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000201:enzymology; D005260:Female; D006084:Graft Rejection / Q000517:prevention & control; D006801:Humans; D007168:IMP Dehydrogenase / Q000378:metabolism*; D007166:Immunosuppressive Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use; D008107:Liver Diseases / Q000601:surgery; D016031:Liver Transplantation / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D007166:Immunosuppressive Agents; D007168:IMP Dehydrogenase; C488211:IMPDH1 protein, human; D009173:Mycophenolic Acid