Clear Filters
Clear Filters

Issues fitting ka parameter

1 view (last 30 days)
Hello,
I have simbiology 2019a. I am trying to fit ka using a one compartment PK model (I have Vd and Cl fixed).
I had previously scanned my model for ka and found that ka should be approximate 0.5. When I compared simulations to observed data, 0.5 allowed for the model to fit the data well.
I next tried fitting the data using the same concentrations in the model simulations. The ka's were much larger than expected. Upon further expection, the generated simulated concentration vs time profile doesn't produce a curve. It appears as if the model fittings are not generating a concentration profile. I checked if I was making a mistake in the dosing information or response information, but my fitting screen is similar to the example (https://www.mathworks.com/help/simbio/gs/fit-data.html)
Any input or additional references to compare would be greatly appreciated.
Thanks
  4 Comments
Peter Bloomingdale
Peter Bloomingdale on 2 May 2019
Edited: Peter Bloomingdale on 2 May 2019
Just a quick comment that may help you. The way you are modeling bioavailability is essentially just changing the rate of absorption.
Dose*F should be incorporated as the initial condition of the gut compartment.
Brett Fleisher
Brett Fleisher on 2 May 2019
Great, thanks for help.
I had uploaded the wrong data set. I've attached for the corrected version for your reference.
Thanks again!

Sign in to comment.

Accepted Answer

Sietse Braakman
Sietse Braakman on 2 May 2019
Hi Brett,
There are three ways you can approach this:
  1. by assuming that the dose is reduced by a factor F, such as Peter suggested above. However, keep in mind that your absorption rate is dependent on the concentration/amount of the drug_depot species. So by reducing the dose amount by a factor F, you also reduce the initial absorption rate.
  2. by assuming that a fraction F of the drug_depot species makes its way to the drug_central species, while a factor (1-F) makes is passed through the intestine without being absorbed. This ensures that the first order rate is not affected by the reduced dose amount. We have an example on bioavailability on our website as well: https://www.mathworks.com/help/simbio/ug/estimating-the-bioavailability-of-a-drug.html.
  3. Get both IV and Oral data and approximate F by F = AUC_Oral/AUC_IV, where AUC is the area under the curve of the drug concentration in the central compartment.
Best,
Sietse

More Answers (1)

Brett Fleisher
Brett Fleisher on 2 May 2019
Hi Sietse,
Thank you again for the help. I've uploaded the model you had helped me with for future reference.
Much appreciated!
Brett

Communities

More Answers in the  SimBiology Community

Categories

Find more on Scan Parameter Ranges in Help Center and File Exchange

Community Treasure Hunt

Find the treasures in MATLAB Central and discover how the community can help you!

Start Hunting!