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Pharmacokinetics of mycophenolic acid in liver transplant patients after intravenous and oral administration of mycophenolate mofetil†
Article first published online: 30 MAY 2007
Copyright © 2007 American Association for the Study of Liver Diseases
Volume 13, Issue 6, pages 791–796, June 2007
How to Cite
Jain, A., Venkataramanan, R., Kwong, T., Mohanka, R., Orloff, M., Abt, P., Kashyap, R., Tsoulfas, G., Mack, C., Williamson, M., Batzold, P. and Bozorgzadeh, A. (2007), Pharmacokinetics of mycophenolic acid in liver transplant patients after intravenous and oral administration of mycophenolate mofetil. Liver Transpl, 13: 791–796. doi: 10.1002/lt.21146
Data were presented at the World Transplant Congress, Boston, July 2006, and partially presented at the American Association for the Study of Liver Diseases, October 2005, Boston and the International Liver Transplant Society, May 2006, Milan.
- Issue published online: 30 MAY 2007
- Article first published online: 30 MAY 2007
- Manuscript Accepted: 21 JAN 2007
- Manuscript Received: 6 OCT 2006
The bioavailability of mycophenolic acid (MPA) after oral administration of mycophenolate mofetil (MMF) has been reported to be more than 90% in healthy volunteers, and in kidney and thoracic organ transplant patients. Such information is limited in liver transplant (LTx) patients. The present study compares the pharmacokinetics of MPA after intravenous (IV) and oral administrations of MMF in LTx recipients. Pharmacokinetic parameters were calculated using WinNonlin software. A total of 12 deceased donor LTx patients initially received IV MMF and were switched to oral MMF after 2-7 days (mean, 3.3 ± 1.7) when oral feeds were started. Multiple blood samples were drawn immediately prior to and after IV or oral MMF and the plasma concentration of MPA was measured. The mean peak plasma concentrations and the area under the plasma concentration vs. time curve (AUC) were significantly higher after IV MMF compared to oral MMF (peak plasma concentrations of 10.7 ± 2.1 μg/mL for IV vs. 4.5 ± 2.8 μg/mL for oral; P = 0.0001; and AUC of 28.9 ± 7.1 μg · hr/mL for IV vs. 12.8 ± 4.2 μg · hr/mL for oral; P = 0.0001). The oral bioavailability of MPA was 48.5 ± 18.7%. The systemic clearance, half-life, and steady state volume of distribution of MPA were 26.9 ± 6 L/hour, 5.5 hours, and 85 liters, respectively. The terminal disposition half-life was not significantly different between the 2 routes of administration. In conclusion, during the early postoperative period, LTx recipients have MPA exposure with oral MMF of less than half that of IV MMF. Use of IV MMF immediately post-LTx may provide an immunological advantage. Liver Transpl 13:791–796, 2007. © 2007 AASLD.