Global Sensitivity Analysis in Physiological Systems

Abstract

Pharmacokinetic models are mathematical models which provide insights into the interaction of chemicals with biological processes. During recent decades, these models have become central of attention in industry that caused to do a lot of efforts to make them more accurate. Current work studies the process of drug and nanoparticle (NPs) distribution throughout the body which consists of a system of ordinary differential equations. We use a tri-compartmental model to study the perfusion of NPs in tissues and a six-compartmental model to study drug distribution in different body organs. We have performed global sensitivity analysis by LHS Monte Carlo method using PRCC. We identify the key parameters that contribute most significantly to the absorption and distribution of drugs and NPs in different organs in body.

Mathematical modeling of vehicle carbon dioxide emissions

“…In order to grasp the impact of model parameters on the system output, we conducted a global sensitivity analysis (GSA) employing partial ranking correlation coefficient (PRCC) which use Latin Hypercube sampling Monte Carlo simulation (LHS). This approach allows us to assess how changes in individual parameters can influence the overall model output [35] , [36] . A positive PRCC indicate a positive correlation between model parameters and its output.…”

A computational analysis of the role of integrins and Rho-GTPases in the emergence and disruption of apical-basal polarization in renal epithelial cells

“…High ranges for variation were chosen, as most of the parameters could not be determined experimentally or derived from previous studies. We varied these 21 parameters in the predefined range (20-500% of the original parameter value) using Latin hypercube sampling to create 3000 samples of parameters space [41][42][43]. A Monte Carlo sampling scheme was used to select 3000 parameter combinations to run simulations in parallel and assess the obtained output results in relation to the prescribed threshold.…”

Application of the Fractional Calculus in Pharmacokinetic Compartmental Modeling

“…Pharmacokinetics models are the main piece of modeling based drug development and can be performed by non-compartmental or compartmental methods. Compartmental modeling helps to find the most efficient route of drug administration based on time of uptake and elimination [1], [2], [3]. These models provide a theoretical and mathematical framework to demonstrate the transmit of molecules biochemistry and transport phenomena in the body, and it has been done by dividing body into two main compartments based on pharmacokinetic and pharmacodynamic of different tissues.…”

“…Therefore, compartmental modeling defines a comprehensive framework which makes an effective drug delivery toward targeted tissue and has been attracted by different researchers to find the most optimized therapy for different diseases such as cancer [4], [5], [6]. These models receives information regarding route of administration such as intravenous or intramuscular injection, and or oral and combine them by different assumptions related to single or multiple doses to demonstrate drug traveling states inside body, starting from the absorbing by tissue and distributing from one organ to the other organ, and then chemical alteration of the specific tissue, and finally declining drug concentration because of elimination of chemical or biochemical drug by all removal paths [1], [2], [3], [4], [5], [6].…”

“…Another approach to simulate distribution of drug in body that involves different organs and their interactions with other tissues called physiologically based pharmacokinetics models (PBPK) [1], [2]. This computer based modeling method receives biological information such as physiological and chemical parameters for administered drug, blood flow rates to different tissues, volume of different organs, absorption and metabolism parameters, exposure and dose parameters and depends on different administration route, predicts the concentration of drug in different tissues using computational and numerical tools [1], [2], [3].…”