Pharmacokinetics of mycophenolic acid in liver transplant patients after intravenous and oral administration of mycophenolate mofetil

Ashokkumar Jain, Raman Venkataramanan, Tai Kwong, Ravi Mohanka, Mark Orloff, Peter Abt, Randeep Kashyap, Georgios Tsoulfas, Cindy Mack, Mary Williamson, Pam Batzold, Adel Bozorgzadeh

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)791-796
Number of pages6
JournalLiver Transplantation
Volume13
Issue number6
DOIs
StatePublished - Jun 1 2007

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Mycophenolic Acid
Intravenous Administration
Oral Administration
Pharmacokinetics
Transplants
Liver
Biological Availability
Area Under Curve
Half-Life

All Science Journal Classification (ASJC) codes

  • Surgery
  • Hepatology
  • Transplantation

Cite this

Jain, Ashokkumar ; Venkataramanan, Raman ; Kwong, Tai ; Mohanka, Ravi ; Orloff, Mark ; Abt, Peter ; Kashyap, Randeep ; Tsoulfas, Georgios ; Mack, Cindy ; Williamson, Mary ; Batzold, Pam ; Bozorgzadeh, Adel. / Pharmacokinetics of mycophenolic acid in liver transplant patients after intravenous and oral administration of mycophenolate mofetil. In: Liver Transplantation. 2007 ; Vol. 13, No. 6. pp. 791-796.
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title = "Pharmacokinetics of mycophenolic acid in liver transplant patients after intravenous and oral administration of mycophenolate mofetil",
abstract = "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.",
author = "Ashokkumar Jain and Raman Venkataramanan and Tai Kwong and Ravi Mohanka and Mark Orloff and Peter Abt and Randeep Kashyap and Georgios Tsoulfas and Cindy Mack and Mary Williamson and Pam Batzold and Adel Bozorgzadeh",
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Jain, A, Venkataramanan, R, Kwong, T, Mohanka, R, Orloff, M, Abt, P, Kashyap, R, Tsoulfas, G, Mack, C, Williamson, M, Batzold, P & Bozorgzadeh, A 2007, 'Pharmacokinetics of mycophenolic acid in liver transplant patients after intravenous and oral administration of mycophenolate mofetil', Liver Transplantation, vol. 13, no. 6, pp. 791-796. https://doi.org/10.1002/lt.21146

Pharmacokinetics of mycophenolic acid in liver transplant patients after intravenous and oral administration of mycophenolate mofetil. / Jain, Ashokkumar; Venkataramanan, Raman; Kwong, Tai; Mohanka, Ravi; Orloff, Mark; Abt, Peter; Kashyap, Randeep; Tsoulfas, Georgios; Mack, Cindy; Williamson, Mary; Batzold, Pam; Bozorgzadeh, Adel.

In: Liver Transplantation, Vol. 13, No. 6, 01.06.2007, p. 791-796.

Research output: Contribution to journalArticle

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T1 - Pharmacokinetics of mycophenolic acid in liver transplant patients after intravenous and oral administration of mycophenolate mofetil

AU - Jain, Ashokkumar

AU - Venkataramanan, Raman

AU - Kwong, Tai

AU - Mohanka, Ravi

AU - Orloff, Mark

AU - Abt, Peter

AU - Kashyap, Randeep

AU - Tsoulfas, Georgios

AU - Mack, Cindy

AU - Williamson, Mary

AU - Batzold, Pam

AU - Bozorgzadeh, Adel

PY - 2007/6/1

Y1 - 2007/6/1

N2 - 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.

AB - 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.

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