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

Abstract

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.

Personalized Therapy for Mycophenolate: Consensus Report by the International Association of Therapeutic Drug Monitoring and Clinical Toxicology

“…The principle of these models is to use first-order absorption with a lag-time chained to 2 or 3 compartment models. 68,[160][161][162]168,169,232,372,377,394,[547][548][549][550][551][552][553][554][555][556][557] More complex models have also been developed, such as the Erlang model that is a simplification of the gamma distribution in which the exponent is an integer that represents the number of virtual transit compartments that the drug has to cross to reach the central compartment, 368,392,558 but they did not always significantly improve the description of MPA profiles. 162 Finally, 1-, 2or more parallel gamma distributions have been able to describe accurately the multiple MPA absorption peaks seen with MMF in various clinical settings.…”

“…68,160,166,168,231,232,377,394,549,551,554,559,560,562 In some studies, the increase in body weight has been reported as increasing MPA oral clearance (CL), in adults 81,155,372,556 and in children. 563 In lung transplantation, CF clearly affects MPA oral bioavailability 162 or CL, 556 whereas when modeling concerned several types of organ transplants in the same analysis, the type of transplant also affected MPA bioavailability and CL. 162,563 Other covariates were more rarely reported, such as weight on the volume of distribution (Vd) in children 164 or creatinine clearance, albumin, sex on Vd, 550,551 MRP2 variants and EC-MPS or MMF formulations on CL, 392 or UGT1A9 variant on absorption and distribution of MPA from EC-MPS.…”

“…Cyclosporine A comedication decreases the enterohepatic circulation and leads to a decreased MPA AUC in comparison with other comedications, particularly tacrolimus.bib68 68,162,169,232,394,549,551,554,562,563 Interestingly, low plasma albumin concentrations and high MPAG concentrations decreased total MPA exposure by reducing MPA binding to albumin but did not seem to have any effect on unbound MPA concentrations. 68,160,166,168,231,232,377,394,549,551,554,559,560,562 In some studies, the increase in body weight has been reported as increasing MPA oral clearance (CL), in adults 81,155,372,556 and in children. 563 In lung transplantation, CF clearly affects MPA oral bioavailability 162 or CL, 556 whereas when modeling concerned several types of organ transplants in the same analysis, the type of transplant also affected MPA bioavailability and CL.…”