SimBiology

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SimBiology implementation of a generic PBPK model. Human fasted, Human fed and Rat physiologies.

Hello, I was wondering if there was a way to model both IV and PO data simultaneously for the same patients using SimBiology; I've successfully fitted the IV data in one model and the PO data using the same model but with different initial estimates, but I was wondering if it's possible to do one fit for both datasets. I get an error when I try to do both because the time course for the IV data and the PO data uses the same scale (0-144 hours) Thanks in advance!

Identification of model (one compartment, two compartments or three compartments) which a drug follows is an important step before population pharmacokinetic modeling. I am aware that the graph between the concentration vs time, gives an idea of the number of compartment a drug follows. But is there a standard way to explore and determine the number of compartment a drug follows in a more objective manner. This would also be helpful to determine the model in which the data needs to be fit. In addition, a note on determining the order of reaction is also welcomed and would make the discussion complete. In Simbiology, is there a standard way to identify the number of compartment a drug follows? Praveen, The model selection is often driven primarily by visualization of data (as you mentioned in your post) and accounting any prior information (if available). In many cases, it is difficult to get clear indication of whether your data follows 2-cmpartment or 1-cmpartment model etc. In these situation, one should try to evaluate both model and compate fits. You can also use AIC/BIC criteria for model selection. I am not aware of any automated tool to compare the model fits in simbiology. It may be useful to have such feature (example one that is available in Phoenix) which can allow to objective function with both model fits, covariate information and GOF plots. SimBiology has a task data comparison tool that allows you to compare different fits (make sure the fits are each saved as task results!) by AIC, BIC, loglikelihood etc., see the screenshots below. <</matlabcentral/discussions/uploaded_files/90/Task%20data%20comparison.png>> <</matlabcentral/discussions/uploaded_files/89/Capture.PNG>> Dear Sietse Braakman, Yes, I use task data comparison for selecting the compartment and for selection of optimization algorithms. Thanks for the guidance. Regards. simbiology population pharmacokinetics pharmacokinetics pharmacology compartment

Non Compartmental Analysis (NCA) is easily performed in Simbiology for drug bolus. With the data imported and selected, selection of Define Plot then Open followed by NCA will directly give the the results of all standard NCA parameters. But suppose my drug is given by infusion, and I want to compute NCA, how to do it? To be more specific, there is no option to to add rate of infusion data in Simbiology during computation of NCA. I have attached a screenshot for better understanding. In the screenshot attached, as you can see there is no option for adding rate of infusion. In this case, is the drug infusion, I suppose is to be considered as drug bolus and then I have to compute NCA. Is this not wrong?

Imports ODE models in the BerkeleyMadonna(TM) format into a SimBiology(R) model

a template PBPK IgG model that can serve as a platform for developing PBPK model for antibodies in tumor bearing mouse

Do you have a good example in Simbiology for me modify the built-in PK models that would create 3 transit compartments prior to absorption. Basically, I would like to create a one-compartmental PK model with 3 transit compartments and then the standard Ka parameter with first order dosing. I then want to do the same for a 2-compartmental PK model with 3 transit compartments prior to absorption. Example 1: V, CL, Ka, MTT and Example 2: Vc, CL, Q, Vp, MTT I attempted to use the gPKPDSim package and thought to use the standard Simbiology interface instead. Andy

In SimBiology I have constructed a simple 2 Compartment Model to describe drug distribution over a set time course. The Model uses 6 parameters. I have a set of 11 individual data sets for the drug, however they are taken from different disease stages (early & late) which can be quantified as the "Time stage of Disease". Previous literature has stated a relationship between the stage of the disease and drug accumulation. However the specific relationship is not known. How do I incorporate the stage of disease as a covariate into my model? I'm unclear how to specify a relationship between the stage and the parameter, most literature says to use a NLME model but again I'm unclear about the implementation of this

I am trying to fit a three compartmental model in MATLAB. Can anyone kindly tell me how to put bounds (lower bound and upper bound) on estimated parameters while fitting the model ? Thanks a lot and really appreciate your help.

Provides a PBPK and a Renin-Angiotensin system model for SimBiology

SimBiology model describing the metabolism and distribution of TCE using a human PBPK model

I have used Simbiology to fit a pharmacokinetic data set (IV bolus administration of a drug to a sample population) to both two- and three-compartment models with linear, first-order rate expressions. Rather than the fit parameters produced by Simbiology (e.g. clearance, inter-compartmental clearance, compartment volumes, etc.), I am most interested in the set of parameters that enter into the poly-exponential equation defining the concentration-time profile. That is the A_i's and alpha_i's in c(t) = \sum_{i=1}^{i=n} A_i exp(-\alpha_i t) for an n-compartment model. Other than deriving or looking up these relationships in a book, is there a way to get Simbiology to produce them with (importantly) their associated error estimates?

I can't seem to find the answer to my question in SimBiology's documentation. Does anyone know how Matlab calculates the non-compartmental AUC? Does it use the linear / log-linear trapezoidal rule? How many points does it use to extrapolate the curve to infinity? Does it use log or linear extension? Many thanks!