Bridging the gap between in silico and in vivo by modeling opioid disposition in a kidney proximal tubule microphysiological system.

ABSTRACT: Opioid overdose, dependence, and addiction are a major public health crisis. Patients with chronic kidney disease (CKD) are at high risk of opioid overdose, therefore novel methods that provide accurate prediction of renal clearance (CL_r) and systemic disposition of opioids in CKD patients can facilitate the optimization of therapeutic regimens. The present study aimed to predict renal clearance and systemic disposition of morphine and its active metabolite morphine-6-glucuronide (M6G) in CKD patients using a vascularized human proximal tubule microphysiological system (VPT-MPS) coupled with a parent-metabolite full body physiologically-based pharmacokinetic (PBPK) model. The VPT-MPS, populated with a human umbilical vein endothelial cell (HUVEC) channel and an adjacent human pr

SUBMITTER: Imaoka T 

PROVIDER: S-EPMC8560754 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature