Population pharmacokinetics of mycophenolic acid in lung transplant recipients with and without cystic fibrosis

作者：Wang Xiao Xing; Feng Meihua R^*; Nguyen Hugh; Smith David E; Cibrik Diane M; Park Jeong M

来源：European Journal of Clinical Pharmacology, 2015, 71(6): 673-679.

DOI：10.1007/s00228-015-1854-7

• Lung transplant
• Cystic fibrosis
• Mycophenolic acid
• Population pharmacokinetics

The objective of this work was to characterize and compare the population pharmacokinetics (PK) mycophenolic acid (MPA) in adult lung transplant recipients with cystic fibrosis (CF) and without the disease (NCF) following repeated oral administration of the prodrug mycophenolate mofetil (MMF) as an immunosuppressant.
Three separate 12-h PK visits were conducted for lung transplant patients with or without CF following repeated MPA treatment with at least a 2-week break between the visits. A population PK model was developed using nonlinear mixed effects modeling (NONMEM), and the contribution of physiological and pathological factors and time dependence of apparent oral clearance (CL/F) were assessed.
For both CF and NCF patients, MPA serum concentration-time profiles were best described by a two-compartment PK model with first-order absorption. CF patients had a slower absorption rate (K-a), and elevated CL/F and volume of distribution (Vd/F) compared with NCF patients. There is a significant contribution of body weight and CF disease to MPA CL/F, and both were included in the final model as covariates.
The population PK model developed from our study successfully characterizes the absorption, distribution, and elimination of MPA in lung transplant recipients with or without CF disease. The decrease of MPA absorption and increase of both oral clearance (CL/F) and volume of distribution (V-2/F and V-3/F) in the CF patients would suggest the importance of MPA therapeutic monitoring for this group.

• 出版日期2015-6