title: Limited-sampling strategy for mycophenolic acid in renal transplant recipients reciving enteric-coated mycophenolate sodium and tacrolimus.
abstract: BACKGROUND
  Substantial research has been conducted to develop limited-sampling strategies (LSS) to estimate the area under the curve (AUC(0-12h)) in patients treated with mycophenolate mofetil. However, no LSS has been validated for enteric-coated mycophenolate sodium (EC-MPS). Our aim was to develop an LSS to measure the AUC(0-12h) of mycophenolic acid in kidney recipients treated with tacrolimus and EC-MPS.
  
  
  METHODS
  Thirteen serial blood samples were collected over 12 hours from 71 patients treated with tacrolimus and EC-MPS. Mycophenolic acid was measured in plasma using the enzyme-multiplied immunoassay. LSSs were developed and validated by multiple regression analysis using a 2-group method (test, n = 47; validation, n = 24).
  
  
  RESULTS
  The best LSS obtained in the test group were for 3 and 4 time points AUC(0-12h) (mg·h(-1)·L(-1)) = 15.99 + 0.87C1 h + 0.68C2 h + 7.85C4 h and AUC(0-12h) (mg·h(-1)·L(-1)) =11.15 + 0.68C1 h + 0.45C1.5 h + 0.57C2 h + 8.16C4 h, respectively. When these LSS were tested in the validation group, the results were acceptable (adjusted r(2) = 0.71, bias =-0.214 [95% confidence interval (CI): -7.91 to 7.48], precision = 7.48 (95% CI: 3.69-19.39) for 3 time points and adjusted r(2) = 0.76, bias = -1.48 (95% CI: -8.23 to 5.27), precision = 7.68 (95% CI: 4.23-13.50) for 4 time points).
  
  
  CONCLUSIONS
  : An LSS using time points at C(1h)-C(2h)-C(4h) or C(1h)-C(1.5h)-C(2h)-C(4h) provides the most reliable and accurate estimation of the AUC(0-12h) of mycophenolic acid in stable renal transplant recipients treated with EC-MPS and tacrolimus.
authors.affiliation: Department of Nephrology, Hospital Clínico Universitario San Carlos, Madrid, Spain. sanchezfruct@telefonica.net
authors.forename: Ana I
authors.initials: AI
authors.lastname: Sánchez Fructuoso
authors.forename: Isabel
authors.initials: I
authors.lastname: Perez-Flores
authors.forename: Natividad
authors.initials: N
authors.lastname: Calvo
authors.forename: Rosalia
authors.initials: R
authors.lastname: Valero
authors.forename: Elisa
authors.initials: E
authors.lastname: Matilla
authors.forename: Dolores
authors.initials: D
authors.lastname: Ortega
authors.forename: Maria A
authors.initials: MA
authors.lastname: Del Dedo
authors.forename: Cristina
authors.initials: C
authors.lastname: Fernández-Pérez
authors.forename: Alberto
authors.initials: A
authors.lastname: Barrientos
mesh_terms: D000328:Adult; D019540:Area Under Curve; D001800:Blood Specimen Collection / Q000379:methods*; D005260:Female; D006801:Humans; D016030:Kidney Transplantation / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000031:analogs & derivatives* / Q000097:blood*; D013608:Tablets, Enteric-Coated; D016559:Tacrolimus / Q000097:blood*
chemical_list: D013608:Tablets, Enteric-Coated; D009173:Mycophenolic Acid; D016559:Tacrolimus