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 microg/mL for IV vs. 4.5 +/- 2.8 microg/mL for oral; P = 0.0001; and AUC of 28.9 +/- 7.1 microg . hr/mL for IV vs. 12.8 +/- 4.2 microg . 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.
authors.affiliation: Department of Surgery, Division of Transplantation, University of Rochester Medical Center, Rochester, NY 14642, USA. ashok_jain@urmc.rochester.edu
authors.forename: Ashok
authors.initials: A
authors.lastname: Jain
authors.forename: Raman
authors.initials: R
authors.lastname: Venkataramanan
authors.forename: Tai
authors.initials: T
authors.lastname: Kwong
authors.forename: Ravi
authors.initials: R
authors.lastname: Mohanka
authors.forename: Mark
authors.initials: M
authors.lastname: Orloff
authors.forename: Peter
authors.initials: P
authors.lastname: Abt
authors.forename: Randeep
authors.initials: R
authors.lastname: Kashyap
authors.forename: Georgios
authors.initials: G
authors.lastname: Tsoulfas
authors.forename: Cindy
authors.initials: C
authors.lastname: Mack
authors.forename: Mary
authors.initials: M
authors.lastname: Williamson
authors.forename: Pam
authors.initials: P
authors.lastname: Batzold
authors.forename: Adel
authors.initials: A
authors.lastname: Bozorgzadeh
mesh_terms: D000284:Administration, Oral; D000328:Adult; D001682:Biological Availability; D005260:Female; D006084:Graft Rejection / Q000517:prevention & control*; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D007275:Injections, Intravenous; D016031:Liver Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D011184:Postoperative Period; D011446:Prospective Studies
chemical_list: D007166:Immunosuppressive Agents; D009173:Mycophenolic Acid