Pharmacokinetic monitoring of mycophenolic acid in heart transplant patients: correlation the side-effects and rejections with pharmacokinetic parameters.

Autor:	Figurski MJ; Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA., Pawiński T, Goldberg LR, DeNofrio D, Nawrocki A, Taylor DO, Lake KD, Chojnowski D, Shaw LM
Jazyk:	angličtina
Zdroj:	Annals of transplantation [Ann Transplant] 2012 Jan-Mar; Vol. 17 (1), pp. 68-78.
DOI:	10.12659/aot.882638
Abstrakt:	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.
Databáze:	MEDLINE
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