title: Free mycophenolic acid should be monitored in renal transplant recipients with hypoalbuminemia.
abstract: The current approach for therapeutic drug monitoring in renal transplant recipients receiving mycophenolate mofetil (MMF) is measurement of total mycophenolic acid (MPA) concentration. Because MPA is highly bound, during hypoalbuminemia the total concentration no longer reflects the free (pharmacologically active) concentration. The authors investigated what degree of hypoalbuminemia causes a significant change in protein binding and thus percentage free MPA. Forty-two renal transplant recipients were recruited for the study. Free and total concentrations of MPA (predose, and 1, 3, and 6 hours post-MMF dose samples) and plasma albumin concentrations were determined on day 5 posttransplantation. Six-hour area under the concentration-time curve (AUC(0-6)) values were calculated for free and total MPA, and percentage free MPA was determined for each patient. The authors found a significant relationship between low albumin concentrations and increased percentage free MPA (Spearman correlation = -0.54, P < 0.0001). Receiver operating characteristic (ROC) curve analysis was performed on the albumin versus percentage free MPA data. The cutoff value of albumin determined from the ROC analysis that differentiated normal from elevated percentage free MPA (defined as > or = 3%) in this patient population was 31 g/L. At this cutoff value albumin was found to be a good predictor of altered free MPA percentage, with a sensitivity and specificity of 0.75 and 0.80, respectively, and an area under the ROC curve of 0.79. To rationalize MMF dosing regimens in hypoalbuminemic patients (plasma albumin < or = 31 g/L), clinicians should consider monitoring the free MPA concentration.
authors.affiliation: School of Pharmacy, University of Queensland, Brisbane, Queensland, Australia. BAtcheson@soms.uq.edu.au
authors.forename: Bronwyn A
authors.initials: BA
authors.lastname: Atcheson
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Taylor
authors.forename: Carl M J
authors.initials: CM
authors.lastname: Kirkpatrick
authors.forename: Stephen B
authors.initials: SB
authors.lastname: Duffull
authors.forename: David W
authors.initials: DW
authors.lastname: Mudge
authors.forename: Peter I
authors.initials: PI
authors.lastname: Pillans
authors.forename: David W
authors.initials: DW
authors.lastname: Johnson
authors.forename: Susan E
authors.initials: SE
authors.lastname: Tett
mesh_terms: D000328:Adult; D000368:Aged; D019540:Area Under Curve; D016903:Drug Monitoring / Q000379:methods*; D005260:Female; D006801:Humans; D034141:Hypoalbuminemia / Q000150:complications / Q000378:metabolism*; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics*; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics*; D011485:Protein Binding; D012680:Sensitivity and Specificity
chemical_list: D007166:Immunosuppressive Agents; D009173:Mycophenolic Acid