Eur J Drug Metab Pharmacokinet. 2025 Feb 1. doi: 10.1007/s13318-025-00936-5. Online ahead of print.
ABSTRACT
BACKGROUND AND OBJECTIVES: As an immunosuppressant, mycophenolate mofetil (MMF) is used to prevent graft versus host disease (GVHD) in patients after hematopoietic stem cell transplantation (HCT). This study aimed to establish a population pharmacokinetic model and simulate the dosage protocol in HCT patients with thalassemia (TM) to fill the gap of lacking MMF dosing regimen.
METHODS: The mycophenolic acid (MPA) plasma concentrations were obtained from HCT patients with TM after using MMF. The population pharmacokinetic (PPK) parameters were obtained by NONMEM (Version VII, Level 2.0; ICON Development Solutions, Ellicott City, MD, USA) program. Monte Carlo simulations were used to determine the optimal dosing.
RESULTS: A total of 239 blood samples from 31 pediatric patients were available, the PPK of MPA was described as a two-compartment model. The typical values for MPA clearance (CL), central distribution volume (V2), peripheral distribution volume (V3), intercompartmental clearance (Q), and absorption rate constant (Ka) were 14.9 L/h, 83.5L, 141L, 3.13 L/h, and 1.37/h respectively. The inter-individual variability (IIV) of CL and V2 were 35% and 41%, respectively. Simulation results suggested that, as the patient’s body surface area (BSA) value increased, MMF dosage initiated from 500 mg twice daily was effective.
CONCLUSIONS: A ‘tiered’ dosage regimen including patient urea and with doses stratified across BSA quartiles, rather than a ‘one dose fits all’ regimen, would help individualize MMF therapy in this population.
PMID:39891881 | DOI:10.1007/s13318-025-00936-5
