Population pharmacokinetics of mycophenolic acid in lung transplant recipients with and without cystic fibrosis
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- 作者：Xiao-Xing Wang ; Meihua R. Feng ; Hugh Nguyen…
- 关键词：Lung transplant ; Cystic fibrosis ; Mycophenolic acid ; Population pharmacokinetics
- 刊名：European Journal of Clinical Pharmacology
- 出版年：2015
- 出版时间：June 2015
- 年：2015
- 卷：71
- 期：6
- 页码：673-679
- 全文大小：379 KB
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Meihua R. Feng (1)
Hugh Nguyen (2)
David E. Smith (1)
Diane M. Cibrik (3)
Jeong M. Park (4)
1. Department of Pharmaceutical Sciences, College of Pharmacy, University of Michigan, 428 Church St, Ann Arbor, MI, 48109, USA
2. College of Pharmacy, University of Michigan, Ann Arbor, MI, 48109, USA
3. Department of Internal Medicine, School of Medicine, University of Michigan, Ann Arbor, MI, 48109, USA
4. Department of Clinical, Social and Administrative Sciences, College of Pharmacy, University of Michigan, Ann Arbor, MI, 48109, USA - 刊物类别：Biomedical and Life Sciences
- 刊物主题：Biomedicine
Pharmacology and Toxicology - 出版者：Springer Berlin / Heidelberg
- ISSN：1432-1041
文摘
Purpose 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. Methods 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. Results 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 (Ka), 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. Conclusions 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 (V2/F and V3/F) in the CF patients would suggest the importance of MPA therapeutic monitoring for this group.