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Population pharmacokinetics of mycophenolic acid in pediatric patients with juvenile dermatomyositis and optimization of limited sampling strategy

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posted on 16.09.2020 by Guangfei Wang, Qiaofeng Ye, Yidie Huang, Jinmiao Lu, Hong Xu, Zhiping Li

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 (AUC0–12 h) was calculated. By removing one sampling point at a time, AUC0–12 h from three-point sampling strategy was re-calculated via Bayesian approach. AUC0–12 h from the three-point sampling strategy (by removing the point at 20 minutes post-dose) had the strongest correlation with AUC0–12 h from the four-point sampling strategy (Pearson’s r = 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 (AUC0–12 h) was calculated. By removing one sampling point at a time, AUC0–12 h from three-point sampling strategy was re-calculated via Bayesian approach. AUC0–12 h from the three-point sampling strategy (by removing the point at 20 minutes post-dose) had the strongest correlation with AUC0–12 h from the four-point sampling strategy (Pearson’s r = 0.971).

Funding

This study was supported by the National Natural Science Foundation of China [No. 81874325], Clinical Pharmacy Key Specialty Construction Project of Shanghai [No. 2017/26] and Scientific Research Project of Science and Technology Commission of Shanghai Municipality [No. 18DZ1910604].

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