title: Validation of limited sampling strategy for estimation of mycophenolic acid exposure during the first year after heart transplantation.
abstract: BACKGROUND
  Individualization of mycophenolate mofetil (MMF) dosing based on mycophenolic acid (MPA) therapeutic drug monitoring may minimize the risk of organ transplant rejection. The MPA area under the 12-hour concentration-time curve (MPA-AUC(0-12h)) is a more powerful predictor of rejection than are MPA trough levels. Measurement of MPA-AUC(0-12h,) however, is difficult and clinically impractical. The limited sampling strategy (LLS) has been proposed to overcome this problem.
  
  
  OBJECTIVE
  To validate the predictive performance of MPA LSS algorithms previously published for heart transplant (HTx) recipients (initial group) when applied to a new independent group of 29 HTx recipients (validation group) during the first year after transplantation.
  
  
  METHODS
  In a previous study, we established 2 algorithms using a LSS in HTx recipients: (1) 5.568 + 0.902 x C(1.25) + 2.022 x C(2) + 4.594 x C(6) and (2) 3.8 + 1.025 . C(1.25) + 1.819 x C(2) + 1.566 x C(4) + 3.479 x C(6). Agreement between abbreviated AUC and the full AUC(0-12h) was tested using the Bland-Altman method. The validation group was used to test and assess bias and precision.
  
  
  RESULTS
  The 2 LSS algorithms used predicted the corresponding MPA-AUC(0-12h) with a mean bias of -4.85% and -3.6% and mean precision of 15.9% and 14%, respectively.
  
  
  CONCLUSIONS
  The MPA-AUC(0-12h) obtained using the LSS may be useful to guide clinical management and dosing. This study prospectively validates 2 algorithms for calculation of MPA-AUC(0-12h) using an LSS calculated in HTx recipients. Bias and precision values suggest that our algorithms could be used for MPA therapeutic drug monitoring predictions in HTx recipients who share the same characteristics.
authors.affiliation: Chair of Pharmacology, Department of Experimental and Clinical Pathology and Medicine, S. Maria della Misericordia University Hospital, P. le S. Maria della Misericordia 15, 33100 Udine, Italy. massimo.baraldo@uniud.it
authors.forename: M
authors.initials: M
authors.lastname: Baraldo
authors.forename: P G
authors.initials: PG
authors.lastname: Cojutti
authors.forename: M
authors.initials: M
authors.lastname: Isola
authors.forename: M T
authors.initials: MT
authors.lastname: Feruglio
authors.forename: V
authors.initials: V
authors.lastname: Tursi
authors.forename: U
authors.initials: U
authors.lastname: Livi
authors.forename: M
authors.initials: M
authors.lastname: Furlanut
mesh_terms: D000328:Adult; D000368:Aged; D000465:Algorithms; D019540:Area Under Curve; D003404:Creatinine / Q000097:blood; D016572:Cyclosporine / Q000627:therapeutic use; D005260:Female; D016027:Heart Transplantation / Q000276:immunology*; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000627:therapeutic use; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000008:administration & dosage* / Q000031:analogs & derivatives* / Q000097:blood / Q000627:therapeutic use; D012044:Regression Analysis; D012709:Serum Albumin / Q000378:metabolism
chemical_list: D007166:Immunosuppressive Agents; D012709:Serum Albumin; D016572:Cyclosporine; D003404:Creatinine; D009173:Mycophenolic Acid