Population pharmacokinetics of mycophenolic acid and dose optimisation in adult Chinese kidney transplant recipients

Abstract

1. This study aimed to establish a population pharmacokinetic (PPK) model of mycophenolic acid (MPA), quantify the effect of clinical factors and pharmacogenomics of MPA, and optimise the dosage for adult kidney transplant recipients.

2. One-hundred and four adult renal transplant patients were enrolled. The PPK model was established using the Phoenix^® NMLE software and the stepwise methods were filtered for significant covariates. Monte Carlo simulations were performed to optimise the dosage regimen.

3. A two-compartment model with first-order absorption and elimination (including lag time) provided a more accurate description of MPA pharmacokinetics. Serum albumin (ALB) significantly affected the central apparent clearance (CL/F), whereas post-transplant time and creatinine clearance were associated with a central apparent volume of distribution (V/F). The estimated population values obtained by the final model were 17.5 L/h and 93.97 L for CL/F and V/F, respectively. Simulation results revealed that larger mycophenolate mofetil doses are required as the ALB concentration decreases. This study established a PPK model of MPA and validated it using various methods. ALB significantly affected CL/F and recommended optimal dose strategies were given based on the final model. These results provide a reference for the personalised therapy of MPA for kidney transplant patients.

Keywords:

• Mycophenolate mofetil
• mycophenolic acid
• PPK
• dose optimisation
• kidney transplantation

Disclosure statement

The authors report no declarations of interest.

Additional information

Funding

The work obtained support from the Jiangxi Provincial Department of Science and Technology (No. 20201BBG71008).