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

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 (R) 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.