Population pharmacokinetics of mycophenolic acid and its glucuronide metabolite in lung transplant recipients with and without cystic fibrosis.
1. Cystic fibrosis (CF) is a disease affecting multiple organs that may reduce the systemic exposure of some drugs. The objective of this work was to characterize and compare the population pharmacokinetics (PK) of the immunosuppressant mycophenolic acid (MPA), and its glucuronide metabolite (MPAG) in adult lung transplant recipients with and without CF (NCF) following repeated oral administration of the prodrug mycophenolate mofetil (MMF). 2. A population PK model was developed, with simultaneous modeling of MPA and MPAG, using nonlinear mixed effects modeling. MPA and MPAG serum concentration-time data were adequately described by a compartmental model including enterohepatic recirculation (EHR). Both MPA and MPAG apparent clearance values were significantly elevated (>65%) in patients with CF (24.1 and 1.95 L/h, respectively) compared to the values in the NCF patients (14.5 and 1.12 L/h, respectively), suggesting a notable influence of CF on MPA absorption and disposition. 3. The population PK model developed from our study successfully characterized the absorption, distribution, elimination and EHR of MPA and the metabolite MPAG in lung transplant recipients with or without CF. This model may help to further understand the impact of CF to the overall clinical effects of MPA therapy including immunosuppression and gastrointestinal side effects.
a Department of Pharmaceutical Sciences and.
Xiao-Xing
XX
Wang
a Department of Pharmaceutical Sciences and.
Wenfang
W
Liu
a Department of Pharmaceutical Sciences and.
Tian
T
Zheng
b Department of Clinical Pharmacy , College of Pharmacy, University of Michigan , Ann Arbor , MI, USA.
Jeong M
JM
Park
a Department of Pharmaceutical Sciences and.
David E
DE
Smith
a Department of Pharmaceutical Sciences and.
Meihua R
MR
Feng
D003550:Cystic Fibrosis / Q000378:metabolism; D020719:Glucuronides / Q000378:metabolism*; D006801:Humans; D007166:Immunosuppressive Agents / Q000493:pharmacokinetics*; D016040:Lung Transplantation; D009173:Mycophenolic Acid / Q000031:analogs & derivatives / Q000493:pharmacokinetics*; D066027:Transplant Recipients / Q000706:statistics & numerical data*
D020719:Glucuronides; D007166:Immunosuppressive Agents; D009173:Mycophenolic Acid
Cystic fibrosis; lung transplant. MPA-7-O-glucuronide; mycophenolic acid; population pharmacokinetics