Population Pharmacokinetics of Mycophenolic Acid: An Update
The most recent comprehensive reviews on the population pharmacokinetics of mycophenolic acid (MPA) were published in 2014. Since then, several population pharmacokinetic studies on MPA have been published. The majority of literature is still focused on the kidney transplant population, although studies have also been conducted in liver and lung transplantation, autoimmune diseases, and hematopoietic stem cell transplant. While the majority of the model building is still based on parametric non-linear mixed-effects modeling, recent studies suggest the suitability of other methodologies. Additionally, instead of just focusing on pharmacokinetic modeling, a trend toward describing the relationships between pharmacokinetic and pharmacodynamic parameters is observed. Given the importance of enterohepatic recirculation (EHR) in the pharmacokinetics of MPA, more authors have attempted to characterize this process in their models. Overall, the recent models have become more sophisticated and incorporate EHR, pharmacodynamic relationships, and metabolites while maintaining many of the population values and covariates identified previously. However, the number of MPA population pharmacokinetic models describing the enteric-coated formulation of MPA (EC-MPA) is still limited. Given the increasing use of EC-MPA, more studies are needed to fill this literature gap. In addition, few studies are yet available characterizing free MPA concentration or MPA metabolites. Given the extensive protein binding, low to intermediate extraction, and intrinsic clearance characteristics of MPA in humans, including these variables would improve the population structural models.
Compliance with Ethical Standards
Conflicts of interest
Tony K. L. Kiang and Mary H. H. Ensom have no conflicts of interests to declare.
No funding was received for the preparation of this article.
- 14.Dong M, Fukuda T, Cox S, de Vries MT, Hooper DK, Goebel J, et al. Population pharmacokinetic–pharmacodynamic modelling of mycophenolic acid in paediatric renal transplant recipients in the early post-transplant period. Br J Clin Pharmacol. 2014;78(5):1102–12.CrossRefPubMedPubMedCentralGoogle Scholar
- 15.de Winter BC, Mathot RA, Sombogaard F, Neumann I, van Hest RM, Doorduijn JK, et al. Differences in clearance of mycophenolic acid among renal transplant recipients, hematopoietic stem cell transplant recipients, and patients with autoimmune disease. Ther Drug Monit. 2010;32(5):606–14.CrossRefPubMedGoogle Scholar
- 17.de Winter BC, Monchaud C, Premaud A, Pison C, Kessler R, Reynaud-Gaubert M, et al. Bayesian estimation of mycophenolate mofetil in lung transplantation, using a population pharmacokinetic model developed in kidney and lung transplant recipients. Clin Pharmacokinet. 2012;51(1):29–39.CrossRefPubMedGoogle Scholar
- 27.Abd Rahman AN, Tett SE, Abdul Gafor HA, McWhinney BC, Staatz CE. Development of improved dosing regimens for mycophenolate mofetil based on population pharmacokinetic analyses in adults with lupus nephritis. Eur J Drug Metab Pharmacokinet. doi: 10.1007/s13318-017-0420-3.
- 29.Li H, Mager DE, Sandmaier BM, Storer BE, Boeckh MJ, Bemer MJ, et al. Pharmacokinetic and pharmacodynamic analysis of inosine monophosphate dehydrogenase activity in hematopoietic cell transplantation recipients treated with mycophenolate mofetil. Biol Blood Marrow Transplant. 2014;20(8):1121–9.CrossRefPubMedPubMedCentralGoogle Scholar