Precision sirolimus dosing in children: The potential for model-informed dosing and novel drug monitoring

Frontiers in Pharmacology

Pharmacology

Kao Tang Ying Moua¹  Kathryn Perkins¹  Deron Johnson²  Guofang Shen³  Peter Curtin³  Jeannine S. McCune³  Arthur Li⁴  Wei Gao⁵ 

[1] Alfred E. Mann School of Pharmacy and Pharmaceutical Sciences, University of Southern California, Los Angeles, CA, United States;Clinical Informatics, City of Hope Medical Center, Duarte, CA, United States;Department of Hematologic Malignancies Translational Sciences, City of Hope, and Department of Hematopoietic Cell Transplantation, City of Hope Medical Center, Duarte, CA, United States;Division of Biostatistics, City of Hope, Duarte, CA, United States;Division of Engineering and Applied Science, Andrew and Peggy Cherng Department of Medical Engineering, California Institute of Technology, Pasadena, CA, United States;

关键词: sirolimus (rapamycin);    pediatrics;    therapeutic drug monitoring (TDM);    sweat;    saliva;    dried blood spots (DBS);    pharmacogenomics;    pharmacometabolomic;   

DOI  :  10.3389/fphar.2023.1126981

 received in 2022-12-18, accepted in 2023-02-14,  发布年份 2023

来源: Frontiers

【 摘 要 】

The mTOR inhibitor sirolimus is prescribed to treat children with varying diseases, ranging from vascular anomalies to sporadic lymphangioleiomyomatosis to transplantation (solid organ or hematopoietic cell). Precision dosing of sirolimus using therapeutic drug monitoring (TDM) of sirolimus concentrations in whole blood drawn at the trough (before the next dose) time-point is the current standard of care. For sirolimus, trough concentrations are only modestly correlated with the area under the curve, with R2 values ranging from 0.52 to 0.84. Thus, it should not be surprising, even with the use of sirolimus TDM, that patients treated with sirolimus have variable pharmacokinetics, toxicity, and effectiveness. Model-informed precision dosing (MIPD) will be beneficial and should be implemented. The data do not suggest dried blood spots point-of-care sampling of sirolimus concentrations for precision dosing of sirolimus. Future research on precision dosing of sirolimus should focus on pharmacogenomic and pharmacometabolomic tools to predict sirolimus pharmacokinetics and wearables for point-of-care quantitation and MIPD.

【 授权许可】

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Copyright © 2023 Shen, Moua, Perkins, Johnson, Li, Curtin, Gao and McCune.