Development of a genetically integrated PBPK model for predicting uric acid homeostasis in humans

บทความในวารสาร

ผู้เขียน/บรรณาธิการ

กลุ่มสาขาการวิจัยเชิงกลยุทธ์

รายละเอียดสำหรับงานพิมพ์

รายชื่อผู้แต่ง: Kaewlin N., Liangruksa M., Laomettachit T.

ปีที่เผยแพร่ (ค.ศ.): 2021

วารสาร: Thai Journal of Mathematics (1686-0209)

Volume number: 19

Issue number: 3

หน้าแรก: 854

หน้าสุดท้าย: 864

จำนวนหน้า: 11

นอก: 1686-0209

URL: https://www.scopus.com/inward/record.uri?eid=2-s2.0-85114855912&partnerID=40&md5=19a57d619d25655de4c38c3caf290e6b

ภาษา: English-Great Britain (EN-GB)

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บทคัดย่อ

Serum uric acid (SUA) balance is mainly regulated by the excretion and reabsorption by the kidneys. Much attention has recently been focused on the genetic variation of renal uric acid transporter genes that affect uric acid homeostasis. Here, we have developed a system of equations to study the human uric acid homeostasis using the physiologically based pharmacokinetic (PBPK) model. The PBPK model incorporates blood flow and tissue compartment of organs to describe how uric acid is distributed within the body. We have also implemented the concept of sub-compartments within the kidneys that allows the model to integrate the genetics of individual patients. We chose to model patients with single nucleotide polymorphisms (SNPs) on the SLC2A9 gene (encoding the urate transporter protein, GLUT9) because the gene variation directly affects the amount of uric acid excreted and reabsorbed by the kidneys. SUA levels predicted from our model simulations of the wild-type and several variants of GLUT9 show good agreement with the experimental observations. Our model development results in a framework for implementing genetic factors as a subsystem of PBPK modeling while giving way to a better representation of human physiology in a highly complex system. © 2021 by TJM.

คำสำคัญ

Physiologically based pharmacokinetic modeling, Uric acid homeostasis