MATLAB: Regarding PK modelling in Simbiology!

pk modellingSimBiology

Hi. I am currently trying to carry out a PK analysis using Simbiology but I am unable to get the results maam. I wanted to ask 1) If under the dose column in the dataset, for eg, 20 mg/kg for 0.02kg mice, the value to input is 20*0.02 milligram dose. 2) If under the concentrations in plasma, I have to enter the lg values obtained from the graph or if I have to convert the lg values to normal values before inputting them into Simbiology. 3) Under parameter estimation, what does Transformation (log by default) mean for the estimated parameters?

Thank you, Sue

Best Answer

Hi, I do not know your model so keep this in mind when reading my answers.

1) In a typical PK model, the input is likely to be 20. Please have a look into your model to find out how the weight of the mouse is taken into account

2) Again this depends on your Simbiology model. Which graph did you use to obtain the plasma concentrations? I would guess that the values are you enter are in normal scale but without seeing the model...

3) This link might be interesting for you in order to understand the log transformation log transformation explanation

Related Solutions

MATLAB: Condition in which one compartment does not affect the mass balance

Hi Kazutaka,

In the example you are following along with (https://www.mathworks.com/help/simbio/ug/model-views.html), the PK part of the model is determined by a one compartment model with linear clearance (the compartment Central, with species Drug_Central and elimination reaction reaction_1). The biophase of the drug is modeled in a separate compartment: Biophase, with species Drug_Biophase, and creation reaction reaction_3 and elimination reaction reaction_2. The assumption in this model is that the drug concentration in the biophase does not affect the drug concentration in the central compartment and thereby the mass balance. This concept is implemented through reaction_3 : the stoichiometry of the reaction (Drug_Central -> Drug_Central + Drug_Biophase) has Drug_Central on both sides of the arrow, ensuring that Drug_Central is not being 'consumed' by the reaction. In other words: the concentration of Drug_Central is not affected by reaction_3 and reaction_3 doesn't show up in the ODEs for Drug_Central. In the diagram, this is illustrated by the dashed line between Drug_Central and reaction_3.

The assumption that the Biophase compartment does or doesn't affect the mass balance is a modeling decision made by the authors of the paper referenced at the bottom of the example page. As such, there is no condition that I can say your model should comply with in order to say that the compartment doesn't affect mass balance. The example merely states how to implement this.

I hope that helps. Let me know if you have further questions.

Best,

Sietse

MATLAB: How does Matlab Simbiology calculate pharmacokinetic (PK) non-compartmental (NCA) area under the curve (AUC)

Hi,

Some of the details of SimBiology's non-compartmental analysis (NCA) depend on the type of data and type of dose. However, the conceptual approach is similar, so I will explain below how SimBiology calculates the AUC for a single dose with an IV bolus dose.

First, SimBiology uses the linear trapezoidal rule to estimate the area under the time-concentration curve until the last concentration measurement. This is denoted as AUC_0_tz in the SimBiology desktop. If time is denoted as t and concentration as y, then the following formula is used:

AUC_0_tz = trapz(t,y);

Next, the final two concentration measurements are used to estimate the terminal rate constant, denoted as Lambda_z in the SimBiology desktop. This is calculated in log-space as follows:

Lambda_z = -((log(y(end)) - log(y(end-1)))/(t(end) - t(end-1)));

The extrapolated area under the curve (from t(end) to infinity) is calculated analytically by assuming exponential decay as y(end)/Lambda_z.

Combining all of these, you can see that the AUC is calculated as

AUC = trapz(t,y) - y(end)*(t(end) - t(end-1))/(log(y(end)) - log(y(end-1)))

Best Answer

Related Solutions

MATLAB: Condition in which one compartment does not affect the mass balance

MATLAB: How does Matlab Simbiology calculate pharmacokinetic (PK) non-compartmental (NCA) area under the curve (AUC)

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