title: Comparison of a new enzymatic assay with a high-performance liquid chromatography/ ultraviolet detection method for therapeutic drug monitoring of mycophenolic acid in adult liver transplant recipients.
abstract: Mycophenolic acid (MPA) is used to prevent graft rejection. The methods used for determining the plasma MPA concentration in liver transplant recipients are the enzyme-multiplied immunoassay technique (EMIT), high-performance liquid chromatography with ultraviolet detection (HPLC-UV), and most recently mass spectrometry. EMIT has been reported to overestimate the MPA concentration by 30% to 35% in comparison with HPLC-UV. Recently, a new automated enzymatic assay based on inosine monophosphate dehydrogenase inhibition has been designed. The aim of the present investigation was to compare this technique with validated HPLC-UV in adult liver transplant recipients treated with tacrolimus or cyclosporine. One hundred seventy-six samples from 50 adult liver transplant recipients were analyzed with both techniques. Patients received mycophenolate mofetil (2 or 3 times daily) coadministered with cyclosporine microemulsion (n = 18) or tacrolimus (n = 32). Samples were drawn over an interdose interval during the early or late posttransplantation period. The Passing-Bablok regression and Bland-Altman plot were used to compare the 2 techniques. The Passing-Bablock regression, calculated from 166 samples, showed very good agreement between the enzymatic assay and the HPLC-UV method: enzymatic assay = 1.0204 (95% confidence interval, 0.9942, 1.0478) x HPLC-UV + 0.0201 (-0.0442, 0.0882). No significant bias was found between the techniques (Bland-Altman plot), and the median relative difference was 2.7% (95% confidence interval, -0.4, 6.6). In conclusion, the enzymatic assay showed an excellent correlation with HPLC-UV. Therefore, this method was proved valid and reliable for the monitoring of the plasma MPA concentration in adult liver transplant recipients treated with cyclosporine microemulsion or tacrolimus.
authors.affiliation: Laboratoire de Pharmacologie-Toxicologie, Service de Pharmacie, GH Cochin-Saint Vincent-de-Paul, Paris, France. benoit.blanchet@cch.aphp.fr
authors.forename: Benoit
authors.initials: B
authors.lastname: Blanchet
authors.forename: Fabrice
authors.initials: F
authors.lastname: Taieb
authors.forename: Filomena
authors.initials: F
authors.lastname: Conti
authors.forename: Halim
authors.initials: H
authors.lastname: Abbas
authors.forename: Idrissa
authors.initials: I
authors.lastname: Seydi
authors.forename: Laura
authors.initials: L
authors.lastname: Harcouet
authors.forename: Alain
authors.initials: A
authors.lastname: Dauphin
authors.forename: Yvon
authors.initials: Y
authors.lastname: Calmus
authors.forename: Michel
authors.initials: M
authors.lastname: Tod
mesh_terms: D000328:Adult; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D016903:Drug Monitoring / Q000379:methods* / Q000592:standards; D017248:Enzyme Multiplied Immunoassay Technique / Q000592:standards; D005260:Female; D006084:Graft Rejection / Q000517:prevention & control; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics; D008099:Liver / Q000378:metabolism*; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics; D014466:Ultraviolet Rays
chemical_list: D007166:Immunosuppressive Agents; D009173:Mycophenolic Acid