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Background and Objectives <p>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.</p> Methods <p>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.</p> Results <p>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 (V<sub>2</sub>), peripheral distribution volume (V<sub>3</sub>), 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 V<sub>2</sub> 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.</p> Conclusions <p>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.</p>

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Dosage Recommendations for Off-label Use of Mycophenolate Mofetil in Pediatric Patients with Thalassemia Undergoing Hematopoietic Stem Cell Transplantation: An Approach Based on Population Pharmacokinetic Studies

  • 期刊论文

  • 发表日期：

    2025年2月1日

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  • Lu-lu Niu,
  • Yong-jun Liu,
  • Yun Wu,
  • Tian-min Huang,
  • Ting-qing Wu,
  • Yang Xiao,
  • Xin Chen,
  • Yi-lin Luo,
  • Tao-tao Liu

摘要

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.