title: Pharmacokinetic monitoring of mycophenolic acid in heart transplant patients: correlation the side-effects and rejections with pharmacokinetic parameters.
abstract: BACKGROUND
  Mycophenolate mofetil is a commonly used immunosuppressant in heart transplantation but pharmacokinetic monitoring is not routinely done. We performed a prospective pilot multi-center trial in de-novo heart transplant recipients to evaluate the pharmacokinetics (PK) of mycophenolic acid (MPA) at multiple time points in the first year following transplant.<br />
  
  
  METHODS
  MPA trough and estimated area-under-the-curve (AUC) values were obtained at multiple visits from 21 enrolled patients. We attempted to correlate the side-effects and rejections with PK parameters.<br />
  
  
  RESULTS
  MPA AUC and trough levels increased modestly over 12 months with substantial inter and intra patient variability. Cardiac rejection was associated with low MPA AUC values with a threshold of <36.2 mg×h/L during the first two post-transplant weeks. A threshold of 2-weeks average MPA trough level of 1.43 mg/L provided a sensitivity 82% and a specificity of 60%.<br />
  
  
  CONCLUSIONS
  Adequate MPA levels are associated with decreased risk of allograft rejection. For patients with Cyclosporine co-immunosuppression, we propose an MPA trough of 1.4 mg/L and an MPA AUC of 36 mg × h/L as threshold values for dose adjustments. We recommend monitoring MPA levels at 1, 2 and 4 weeks, 6 months, 1 year and whenever an unexplained side-effect or allograft rejection occurs. Additional MPA AUC measurements are recommended when trough levels do not explain the clinical picture.<br />
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Michał J
authors.initials: MJ
authors.lastname: Figurski
authors.forename: Tomasz
authors.initials: T
authors.lastname: Pawiński
authors.forename: Lee R
authors.initials: LR
authors.lastname: Goldberg
authors.forename: David
authors.initials: D
authors.lastname: DeNofrio
authors.forename: Artur
authors.initials: A
authors.lastname: Nawrocki
authors.forename: David O
authors.initials: DO
authors.lastname: Taylor
authors.forename: Kathleen D
authors.initials: KD
authors.lastname: Lake
authors.forename: Donna
authors.initials: D
authors.lastname: Chojnowski
authors.forename: Leslie M
authors.initials: LM
authors.lastname: Shaw
mesh_terms: D000328:Adult; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D016572:Cyclosporine / Q000008:administration & dosage; D000077561:Daclizumab; D005260:Female; D006084:Graft Rejection / Q000209:etiology; D016027:Heart Transplantation / Q000009:adverse effects / Q000502:physiology; D006801:Humans; D007074:Immunoglobulin G / Q000008:administration & dosage; D007166:Immunosuppressive Agents / Q000009:adverse effects* / Q000493:pharmacokinetics*; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000008:administration & dosage / Q000009:adverse effects* / Q000031:analogs & derivatives / Q000493:pharmacokinetics*; D011446:Prospective Studies; D016559:Tacrolimus / Q000008:administration & dosage
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D007074:Immunoglobulin G; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D000077561:Daclizumab; D009173:Mycophenolic Acid; D016559:Tacrolimus