Open AccessEstimation of The Main Effect and Total Effect of a PBPK Model Based on The Uncertainty of Individual Parameter for Treatment Planning in PSMA Therapy
Author(s) -
A. D. Widyanugraha,
Nur Atikah,
Deni Hardiansyah
Publication year - 2021
Publication title -
iop conference series. earth and environmental science
Language(s) - English
Resource type - Journals
eISSN - 1755-1307
pISSN - 1755-1315
DOI - 10.1088/1755-1315/913/1/012101
Subject(s) - sobol sequence , physiologically based pharmacokinetic modelling , pharmacokinetics , sensitivity (control systems) , mathematics , analysis of covariance , biological system , chemistry , pharmacology , statistics , medicine , biology , engineering , monte carlo method , electronic engineering
The purpose of this study was to identify the most important physiologically-based pharmacokinetic (PBPK) model parameters determining the absorbed dose (AD) in prostate-specific membrane antigen (PSMA) therapy. The extended-Sobol’ global sensitivity analysis method was used to analyze the sensitivity of the PBPK model parameters obtained from 3 patients. The investigated PBPK model parameters were the blood flow to the organs, PSMA binding rate, biological release rates, and density of organs receptor. The outputs of extended Sobol method were the main effect Si and the total effect S Ti of the parameter of interests for each ADs. The sampling strategy of extended Sobol has been implemented based on the mean and covariance matrix of the parameters. From the simulations, the most important parameters which determine the ADs to the kidney was the kidney receptor density (Si=0,4, S Ti =0,8). For tumors, it was shown that tumor receptor density was the most essential parameter (Si=0,7, S Ti =0,8). In conclusion, measurement of the blood flow and organ receptor densities might be of interest to improve individualized treatment of PSMA therapy.