title: Comparison of the Emit immunoassay with HPLC for therapeutic drug monitoring of mycophenolic acid in pediatric renal-transplant recipients on mycophenolate mofetil therapy.
abstract: BACKGROUND
  HPLC is currently the preferred method for accurate measurement of mycophenolic acid (MPA). This study was designed to validate the Emit compared with HPLC in relation to clinical outcome measurements.
  
  
  METHODS
  Pediatric renal-transplant recipients (n = 50) on an immunosuppressive triple regimen consisting of cyclosporin A, prednisone, and mycophenolate mofetil (600 mg/m(2) twice per day) were investigated in an open-label prospective study. Pharmacokinetic profiles over 12 h were obtained at 1 week, 3 weeks, 3 months, and 6 months posttransplant. Plasma MPA was measured by both reversed-phase HPLC and the Emit immunoassay.
  
  
  RESULTS
  There was an association between the risk of acute rejection episodes and low area under the curve values from t(0) to t(12h) (AUC(0-12)) for MPA (MPA-AUC(0-12)) or predose concentrations of MPA derived from both HPLC and Emit measurements. According to ROC analysis, an AUC value of 33.8 mg x h/L for MPA from t(0) to t(12h) (MPA-AUC(0-12)) determined by HPLC had a diagnostic sensitivity of 80% and a diagnostic specificity of 57%. The corresponding value of the Emit was 36.1 mg x h/L. For the predose concentration (MPA-c(12)), a concentration of 1.2 mg/L determined by HPLC and 1.4 mg/L determined by Emit gave a sensitivity of 80% and a specificity of 60%, respectively. There was no association of any pharmacokinetic variables derived from total MPA measurements with an increased risk of side effects related to mycophenolate mofetil.
  
  
  CONCLUSIONS
  The Emit assay appears to have a comparable diagnostic efficacy to HPLC for assessing the risk of acute rejection in pediatric renal-transplant recipients. However, because of the cross-reactivity of the antibody used in the Emit assay with the active MPA acyl glucuronide metabolite, the decision thresholds for the Emit were higher than those calculated from HPLC measurements.
authors.affiliation: Division of Pediatric Nephrology, University Children's Hospital, Im Neuenheimer Feld 150, 69120 Heidelberg, Germany.
authors.forename: Lutz T
authors.initials: LT
authors.lastname: Weber
authors.forename: Maria
authors.initials: M
authors.lastname: Shipkova
authors.forename: Victor W
authors.initials: VW
authors.lastname: Armstrong
authors.forename: Natalie
authors.initials: N
authors.lastname: Wagner
authors.forename: Ekkehard
authors.initials: E
authors.lastname: Schütz
authors.forename: Otto
authors.initials: O
authors.lastname: Mehls
authors.forename: Lothar B
authors.initials: LB
authors.lastname: Zimmerhackl
authors.forename: Michael
authors.initials: M
authors.lastname: Oellerich
authors.forename: Burkhard
authors.initials: B
authors.lastname: Tönshoff
mesh_terms: D000293:Adolescent; D019540:Area Under Curve; D002648:Child; D002675:Child, Preschool; D002851:Chromatography, High Pressure Liquid; D016572:Cyclosporine / Q000627:therapeutic use; D016903:Drug Monitoring / Q000379:methods; D004359:Drug Therapy, Combination; D005260:Female; D005938:Glucocorticoids / Q000627:therapeutic use; D006084:Graft Rejection / Q000517:prevention & control; D006801:Humans; D007118:Immunoassay; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000097:blood* / Q000627:therapeutic use; D016030:Kidney Transplantation; D008297:Male; D009173:Mycophenolic Acid / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000097:blood* / Q000627:therapeutic use; D011241:Prednisone / Q000627:therapeutic use; D011446:Prospective Studies
chemical_list: D005938:Glucocorticoids; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D009173:Mycophenolic Acid; D011241:Prednisone