![]() Usually, we used the Bayesian hierarchical modeling approach to do the model calibration.īefore we apply this method, we need to have the prior knowledge for the model parameters. Prior knowledge (expertise or historical data) So, the next step is to apply our model to make the prediction with our data. We have population PK data and we also construct the PBPK model. The advantage of PBPK model is we can use this model to make additional application such as population PBPK modeling. It can be applied to drug discovery and development and risk assessment.Ĭharacterizing PK parameters for populations So people developed the PBPK that include physiological and physicochemical parameters that correspond to the real-world situation and can be used to describe the complex ADME processes. Sometimes we need to consider the complex mechanism and factors that can help us make a good prediction. bolder processes.īut the real world is not as simple as we think. bolder descriptions of the phenomena involved in the complex. # Physiologically-Based Pharmacokinetic (PBPK) Model We can also used Michaelis-Menten kinetics constants to define the concentration-dependent rate constant for metabolism. Then, we can set up the parameters such as absorption,elimination rate constant. We can set up input dose and define the output such as chemical concentration in blood or other tissue organs. The basic model is constructed by a single variable with few parameters. Therefore, we need to use toxicokinetic modeling. `\(K_m\)`: Concentration of chemical achieve half `\(V_\)` (mass/vol.)īut it’s difficult to realize the whole time-concentration relationship due to it will take a lot of time and money in the experiment. large] the **cumulative does** by constructed **compartmental model**. It’ll go up after intake the drug and then go down after reach the maximum concentration. So we focus on the time and concentration. Kinetics is a branch of chemistry which describe the change of one or more variables as a function of time. It is used to describe the fate of the chemical in a living organism when chemical enter into the animal body. Some people here already know pharmacokinetic. Now, we can move on to the today’s first topic. bolderlimination - How it leave the body? bolderetabolism - How is it broken down and transformation? bolderistribution - Which tissue organ it will go? The fate of chemical in a living organism Some people use the model to estimate the chemical cumulation in the animal body and predict health effect.Īlso, we can integrate the chemical exposure and health effect to assess human health risk. Some people use the model to do "in-vitro in-vivo extrapolation". We want to use this mathematical or statistical model to make some prediction with experimental data. So I used this question in the beginning. I think most people here are very experienced in laboratory experiments like in-vivo or in-vitro.īut I have no idea how many people understand why we need to do computational modeling in our study. # Applying a Global Sensitivity Analysis Workflow to Improve the Computational Efficiencies in Physiologically-Based Pharmacokinetic Modeling Applying a Global Sensitivity Analysis Workflow to Improve the Computational Efficiencies in Physiologically-Based Pharmacokinetic ModelingĬlass: center, middle, inverse, title-slide ![]()
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