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

✍ Scribed by Benoit Blanchet; Fabrice Taieb; Filomena Conti; Halim Abbas; Idrissa Seydi; Laura Harcouet; Alain Dauphin; Yvon Calmus; Michel Tod

• Publisher: John Wiley and Sons
• Year: 2008
• Tongue: English
• Weight: 181 KB
• Volume: 14
• Category: Article
• ISSN: 1527-6465
• DOI: 10.1002/lt.21607

✦ Synopsis

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 ϭ 18) or tacrolimus (n ϭ 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 ϭ 1.0204 (95% confidence interval, 0.9942, 1.0478) ϫ HPLC-UV ϩ 0.0201 (Ϫ0.0442, 0.0882). No significant bias was found between the techniques (Bland-Altman plot), and the median relative difference was 2.7% (95% confidence interval, Ϫ0.4, 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.