Pharmacokinetic monitoring of mycophenolic acid in heart transplant patients: Correlation the side-effects and rejections with pharmacokinetic parameters
Michał J. Figurski, Tomasz Pawiński, Lee R. Goldberg, David DeNofrio, Artur Nawrocki, David O. Taylor, Kathleen D. Lake, Donna Chojnowski, Leslie M. Shaw
Ann Transplant 2012; 17(1): 68-78
Available online: 2012-03-31
Background: Mycophenolate mofetil is a commonly used immunosuppressant in heart transplantation but pharmacokinetic monitoring is not routinely done. We performed a prospective pilot multi-center trial in de-novo heart transplant recipients to evaluate the pharmacokinetics (PK) of mycophenolic acid (MPA) at multiple time points in the first year following transplant.
Material/Methods: MPA trough and estimated area-under-the-curve (AUC) values were obtained at multiple visits from 21 enrolled patients. We attempted to correlate the side-effects and rejections with PK parameters.
Results: MPA AUC and trough levels increased modestly over 12 months with substantial inter and intra patient variability. Cardiac rejection was associated with low MPA AUC values with a threshold of <36.2 mg×h/L during the first two post-transplant weeks. A threshold of 2-weeks average MPA trough level of 1.43 mg/L provided a sensitivity 82% and a specificity of 60%.
Conclusions: Adequate MPA levels are associated with decreased risk of allograft rejection. For patients with Cyclosporine co-immunosuppression, we propose an MPA trough of 1.4 mg/L and an MPA AUC of 36 mg × h/L as threshold values for dose adjustments. We recommend monitoring MPA levels at 1, 2 and 4 weeks, 6 months, 1 year and whenever an unexplained side-effect or allograft rejection occurs. Additional MPA AUC measurements are recommended when trough levels do not explain the clinical picture.
Keywords: Heart Transplant, Pharmacokinetics, Mycophenolate Mofetil, Rejection, clinical outcome, therapeutic drug monitoring