Best single time points to predict the area-under-the-curve in long-term heart transplant patients taking mycophenolate mofetil in combination with cyclosporine or tacrolimus
| Autor: | Renzo Cecere, Nadia Giannetti, Marcelo Cantarovich, Vartan Mardigyan, Besner Jg |
|---|---|
| Rok vydání: | 2004 |
| Předmět: |
Pulmonary and Respiratory Medicine
Adult medicine.medical_specialty Time Factors Heart Diseases medicine.medical_treatment Calcineurin Inhibitors Urology Mycophenolic acid Tacrolimus Heart Neoplasms medicine Humans Drug Interactions Enzyme Inhibitors Aged Heart transplantation Transplantation medicine.diagnostic_test business.industry Area under the curve Middle Aged Mycophenolic Acid Ciclosporin Kidney Transplantation Surgery Calcineurin Therapeutic drug monitoring Area Under Curve Cyclosporine Heart Transplantation Drug Monitoring Cardiology and Cardiovascular Medicine business Cardiomyopathies Immunosuppressive Agents medicine.drug |
| Zdroj: | The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation. 24(10) |
| ISSN: | 1557-3117 |
| Popis: | Background The use of C 2 levels for therapeutic drug monitoring (TDM) of cyclosporine microemulsion (CsA) has been clinically validated. Routine TDM of tacrolimus and mycophenolate mofetil (MMF) is based on trough (C 0 ) levels and side effects, respectively. The purpose of the present study was to determine the best single time points to assess the area-under-the-curve (AUC 0–12 hours ) in long-term heart transplant patients being treated with MMF in combination with CsA or tacrolimus. Methods We studied the AUC 0–12 hours in long-term (>1 year), adult heart transplant patients being treated with CsA and MMF (14 patients) and with tacrolimus and MMF (9 patients). Results C 2 is the best surrogate ( r 2 = 0.87) of CsA AUC 0–12 hours . Tacrolimus C 1 ( r 2 = 0.78), C 2 ( r 2 = 0.83), C 3 ( r 2 = 0.89) and C 4 ( r 2 = 0.92) correlate better than C 0 ( r 2 = 0.51) with the AUC 0–12 hours . When MMF is combined with CsA, there is poor correlation ( r 2 ) of MPA at all measured time points (C 0 = 0.49, C 2 = 0.09, C 3 = 0.23, C 4 = 0.44, and C 6 = 0.60). When MMF is combined with tacrolimus, MPA C 2 ( r 2 = 0.72), C 4 ( r 2 = 0.86), C 6 ( r 2 = 0.85), and C 8 ( r 2 = 0.93) are better surrogates of the AUC 0–12 hours compared with C 0 ( r 2 = 0.69). Conclusion Our results suggest that in long-term heart transplant patients, the calcineurin inhibitor used in combination with MMF affects the correlation between MPA single time points and the AUC 0–12 hours . Future studies should determine the clinical benefit of TDM of tacrolimus and MPA with C 2 or C 4 compared with C 0 and determine the therapeutic ranges. As for CsA-treated patients, CsA TDM should be performed with C 2 , and the TDM of MMF may be clinically irrelevant. |
| Databáze: | OpenAIRE |
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