1. 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
- Author
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Alain Dauphin, Yvon Calmus, Halim Abbas, Michel Tod, Filomena Conti, Benoit Blanchet, Fabrice Taieb, Laura Harcouet, and Idrissa Seydi
- Subjects
chemistry.chemical_classification ,Transplantation ,Chromatography ,Hepatology ,medicine.diagnostic_test ,business.industry ,medicine.medical_treatment ,Liver transplantation ,Mycophenolate ,Tacrolimus ,Confidence interval ,Mycophenolic acid ,Enzyme ,chemistry ,Therapeutic drug monitoring ,IMP dehydrogenase ,medicine ,Surgery ,business ,medicine.drug - 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) × 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. Liver Transpl 14:1745–1751, 2008. © 2008 AASLD.
- Published
- 2008