Population pharmacokinetics of mycophenolic acid in pediatric patients with juvenile dermatomyositis and optimization of limited sampling strategy
Creators: name: Wang, Guangfei
name: Ye, Qiaofeng
name: Huang, Yidie
name: Lu, Jinmiao
name: Xu, Hong
name: Li, Zhiping
Publisher: name: Taylor & Francis
Year: 2020
Subjects: subject: Medicine
subject: Microbiology
subject: FOS: Biological sciences
subject: Environmental Sciences not elsewhere classified
subject: Chemical Sciences not elsewhere classified
subject: Ecology
subject: Immunology
subject: FOS: Clinical medicine
subject: Biological Sciences not elsewhere classified
subject: Cancer
subject: Hematology

description: Juvenile dermatomyositis (JDM) is a rare systemic autoimmune disease specifically affecting children. Mycophenolate mofetil (MMF) is an immunosuppressant used to treat JDM. Mycophenolic acid (MPA) is an active metabolite of MMF. This study aimed to develop a population pharmacokinetic (PPK) model of MPA in children with JDM and optimize the limited sampling strategy (LSS).Fifteen JDM patients treated with MMF, at a median age of 7.35 (range, 3.09–16.1) years, were included. Blood samples were collected at 30 minutes pre-dose, 20 minutes, 60 minutes and 180 minutes post-dose to measure the MPA concentrations. Data were retrospectively collected from the electronic medical records. A two-compartment model with first-order absorption, lag time in absorption, and first-order elimination was developed. Height and co-administered cotrimoxazole were added as the covariates to the model.Concentrations at different time points were simulated and area under the concentration–time curve (AUC<sub>0–12 h</sub>) was calculated. By removing one sampling point at a time, AUC<sub>0–12 h</sub> from three-point sampling strategy was re-calculated via Bayesian approach. AUC<sub>0–12 h</sub> from the three-point sampling strategy (by removing the point at 20 minutes post-dose) had the strongest correlation with AUC<sub>0–12 h</sub> from the four-point sampling strategy (Pearson’s <i>r</i> = 0.971). Juvenile dermatomyositis (JDM) is a rare systemic autoimmune disease specifically affecting children. Mycophenolate mofetil (MMF) is an immunosuppressant used to treat JDM. Mycophenolic acid (MPA) is an active metabolite of MMF. This study aimed to develop a population pharmacokinetic (PPK) model of MPA in children with JDM and optimize the limited sampling strategy (LSS). Fifteen JDM patients treated with MMF, at a median age of 7.35 (range, 3.09–16.1) years, were included. Blood samples were collected at 30 minutes pre-dose, 20 minutes, 60 minutes and 180 minutes post-dose to measure the MPA concentrations. Data were retrospectively collected from the electronic medical records. A two-compartment model with first-order absorption, lag time in absorption, and first-order elimination was developed. Height and co-administered cotrimoxazole were added as the covariates to the model. Concentrations at different time points were simulated and area under the concentration–time curve (AUC<sub>0–12 h</sub>) was calculated. By removing one sampling point at a time, AUC<sub>0–12 h</sub> from three-point sampling strategy was re-calculated via Bayesian approach. AUC<sub>0–12 h</sub> from the three-point sampling strategy (by removing the point at 20 minutes post-dose) had the strongest correlation with AUC<sub>0–12 h</sub> from the four-point sampling strategy (Pearson’s <i>r</i> = 0.971).