PII-084 - POPULATION PHARMACOKINETICS OF MYCOPHENOLATE MOFETIL IN PEDIATRIC ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION PATIENTS.

H. Park¹, K. Hong¹, N. Han², I. Kim¹, H. Kang¹, J. Oh¹; ¹Seoul National University, Seoul, Republic of Korea, ²Jeju National University, Jeju, Republic of Korea.

Background: Mycophenolate mofetil (MMF) is recommended for acute graft-versus-host disease (aGVHD) prophylaxis after hematopoietic stem cell transplantation (HSCT). To date, the population pharmacokinetics of MMF in pediatric HSCT patients have not been solely assessed and MMF dosing is not optimally administered based on pharmacokinetic monitoring. This study aimed to develop population pharmacokinetic model for oral MMF in pediatric HSCT patients and evaluate the influence of clinical covariates on the pharmacokinetic parameters.

Methods: A total of 16 pediatric HSCT patients received oral MMF 15-20 mg/kg twice daily for aGVHD prophylaxis and 64 mycophenolic acid (MPA) concentrations were collected. Clinical data were collected prospectively. A population pharmacokinetic analysis was conducted using nonlinear mixed-effects modeling method. Demographic and clinical data were assessed as covariate using the stepwise covariate method. The final model was evaluated and validated for its robustness using a goodness-of-fit plot and a bootstrap method.

Results: A final one-compartment model with first-order absorption accurately described the population pharmacokinetics of MPA. The population parameter estimates for absorption rate constant (Ka), volume of distribution (Vd/F), and apparent clearance (CL/F) were 5.06 h-1, 82.1 L, and 18.3 L/h. Body surface area (BSA) had a significant impact on the Vd/F of MPA.

Conclusion: This study allowed estimation of population pharmacokinetic parameters of MPA in pediatric HSCT patients. This MMF PopPK model will be a basis for BSA-based individualized therapy in pediatric HSCT patients in optimizing pediatric patient outcomes.