Pharmacokinetic Evaluation of Mycophenolic Acid Proﬁles During the Period Immediately Following an Orthotopic Liver Transplant D. Fatela-Cantillo, R. Hinojosa-Pérez, M.I. Peralvo-Rodríguez, J. Serrano-Díaz Canedo, and M.A. Gómez-Bravo ABSTRACT Background. Area under the curve (AUC) limited sampling strategies have been proposed to improve the efﬁciency of mycophenolic acid (MPA), treatment of the transplanted patient. Our objective was to develop a model in the initial phase of the transplantation that explains the variability in the pharmacokinetic behavior of MPA in the immediate posttransplant period, following treatment with mycophenolate mofetil (MMF) in adult liver transplantation. Methods. One hundred ten pharmacokinetic simpliﬁed sampling proﬁles were collected, including four samples over a 6-hour postdose interval, in over 60 patients treated with cyclosporine or tacrolimus, MMF, and steroids, combining Daclizumab in more than a third of the patients. For an enzyme-multiplied immunoassay technique method was established for MPA estimates. The correlation between the AUC and the plasma concentration points was established using a multiple linear regression with various equations for three different pharmacokinetic groups. Results. The maximum mean values of MPA AUC and predose concentration (C0h) (20.8  11.8 and 2.3  1.8, respectively) were reached on the third day. The single sample showing the greatest correlation with the MPA AUC was the one collected after 3 hours (r 2 = 0.575); 59.1% of proﬁles displayed a single peak with more than half showing a tmax  3 hours. Conclusions. This proﬁle analysis during the ﬁrst few weeks highlighted the problems in determining therapeutic targets. Proﬁles showing a double peak revealed the marked inﬂuence of the enterohepatic cycle on MPA concentrations during the initial phase. A T PRESENT, the incidence of acute cellular rejection has been reduced due in part to new immunosuppres- sive combinations. 1 Mycophenolate mofetil (MMF) is com- monly used in these new regimens. 2,3 Its high pharmacoki- netic variability and unpredictable behavior, mainly during the transplant induction phase, have resulted in the need to ﬁnd new tools to optimize dosage prescriptions. The mul- ticenter clinical trials (FDCC OptiCept, APOMGYE) sought to demonstrate an effective and rational basis for adjusting MMF doses based on mycophenolic acid (MPA) concentrations. Plasma level monitoring protocols 8 have included strategies for limited sampling strategies to calcu- late the MPA area under the curve (AUC), which is of greater clinical use compared to the predose concentration (C0h). AUC is a better indicator of the efﬁciency and safety of the medication in the transplanted patient. However, it is not commonly used, in all probability because it is difﬁcult to interpret, cumbersome to perform, and varies greatly among types of transplants. The objective of this study was to use an abbreviated sampling model of MPA AUC in the immediate post–liver transplant period to individualize drug doses. From the Department of Clinical Biochemistry, Emergency and Intensive Care Unit and Surgical Hepato-Pancreato-Biliary Unit, Virgen del Rocı´o University Hospitals, Seville, Spain. Address reprint requests to Daniel Fatela-Cantillo, Department of Clinical Biochemistry, Ediﬁcio de Laboratorios 4 a Planta, Hospitales Universitarios Virgen del Rocío, Avenida de Manuel Siurot s/n, 41013, Seville, Spain. E-mail: danielfatela@yahoo.es 0041-1345/06/$–see front matter © 2006 by Elsevier Inc. All rights reserved. doi:10.1016/j.transproceed.2006.08.076 360 Park Avenue South, New York, NY 10010-1710 2482 Transplantation Proceedings, 38, 2482–2485 (2006)