Pharmacokinetics of enteric-coated mycophenolate sodium in stable liver transplant recipients

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Clinical Transplantation

Volume 21 Issue 3 Page 413 - May/June 2007

Clinical Transplantation 21 (3), 413–416. doi:10.1111/j.1399-0012.2007.00662.x

Pharmacokinetics of enteric-coated mycophenolate sodium in stable liver transplant recipients

Theodore W. , Uwe Christians, F. Trotter and Bendrick-Peart

Division of Gastroenterology/Hepatology, Department of Anesthesiology, University of Colorado Health Sciences Center, Denver, CO, USA

Trotter MD, Division of Gastroenterology/Hepatology, Department of Anesthesiology, University of Colorado Health Sciences Center, 4200 E. 9th Avenue, B-154, Denver, CO 80262, USA.Tel.: +1 ; fax: +1 ;e-mail: james.trotter@...

TW, Christians U, Trotter JF, Bendrick-Peart J. Pharmacokinetics of enteric-coated mycophenolate sodium in stable liver transplant recipients.Clin Transplant 2007: 21: 413–416. © Blackwell Munksgaard, 2007

Abstract

Introduction: Mycophenolate mofetil (MMF) is one of the major immunosuppressive agents used in liver transplantation recipients. In an attempt to mitigate one of the most common side effects of MMF (gastrointestinal symptoms), enteric-coated mycophenolate sodium (EC-MPS) was developed. In this study, we report the pharmacokinetic profile of EC-MPS in stable liver transplantation recipients administered a single 720 mg dose.

Methods: Liver transplantation recipients more than one yr after transplantation were administered a single dose of 720 mg EC-MPS after which blood levels of MPA were measured at frequent intervals using a specific and validated LC-MS/MS assay.

Results: The characteristics of the 21 patients studied were: mean age was 55.9 yr, 13 were female, eight had hepatitis C, and 14 were on tacrolimus. The mean apparent half-life of MPA was 5.3 ± 4.3 h, (1.0–15.7). Mean tmax was 2.4 ± 1.1 h (1.0–5.0). The mean area-under-curve was 45.3 ± 23.1 μg-h/mL (17.3–90.0). Trough level concentrations (C12 h) showed large inter-individual variability (0–9.2 μg/mL). There was no difference in any of the pharmacokinetic parameters relative to: gender, HCV, administration of tacrolimus vs. cyclosporine or type of biliary anastomosis.

Conclusions: There is a wide variation in pharmacokinetic parameters in stable, long-term liver transplantation recipients receiving a single dose of EC-MPS. These data suggest that therapeutic drug monitoring with EC-MPS may have limited utility in liver transplantation recipients.