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Mimicking Urination in PKsim/MoBi #275

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Tpa3 opened this Issue Jan 22, 2019 · 5 comments

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@Tpa3
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Tpa3 commented Jan 22, 2019

Hi everyone,
First off thanks for making such great pieces of software that I use almost every day.

I have a few questions regarding Urine concentrations of compounds in PKsim.

I have built a model for a compound and verified the results against plasma data. However, I was also given measured urine concentrations of the compound and would like to further verify the model against this data.

From what I can tell the Urine compartment holds the total amount of the removed compound from the blood in PKsim with a static volume and the compound is never removed from the urine compartment. The total amount would work great most of the time, unfortunately this won’t work for my dataset.

I was wondering if there was a way to simulate the removal of the compound from the compartment to mimic urination in PKsim or MoBi.

If I can simply remove a percentage of the compound from the compartment at specified times after administration this would suffice to get a rough estimate. Is this something I could do in the Events Building block in MoBi? I could then presumably re-write the Urine compartment’s formula for volume as increasing a function with time that resets after urination occurs.

Thank you!

TlDr:
Is there a way to simulate the sudden removal of a compound from the Urine compartment in PKsim or MoBi to mimic urination? If I could remove a certain percentage of the compound from the compartment at specified times I would be a very happy camper.

@msevestre msevestre added the question label Jan 22, 2019

@HenrikCordes

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HenrikCordes commented Jan 28, 2019

Dear @Tpa3 ,

as far as I know there is no removal form the urine compartment in PK-Sim. The predefined observer are the total amount and concentration (Urine volume by default is 1 L).

From what I can tell the Urine compartment holds the total amount of the removed compound from the blood in PKsim with a static volume and the compound is never removed from the urine compartment. The total amount would work great most of the time, unfortunately this won’t work for my dataset.

Why not? What do you want so simulate? How does your data look like?

If you have data that does not fit to PK-Sim observers (output), in general you have 2 options:

  1. Build that observer in MoBi
  2. Normalize / convert your data into the observer units

An example for 2) would be:
If you have urine concentration data from different samples you could use the sample volume to calculate the total amount in your sample (n1=c1V1, n2=c2V2, etc.). By cumulative addition of these values you would have the data for the observer "total amount" in urine (n1 = n1, n2 = n1+n2,...).

Hope this helps!

@sfrechen

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sfrechen commented Jan 31, 2019

Yes, I would follow the proposal of Henrik: adjust your data so that they can be compared with the default PK-Sim observer (concentration in urine, which is actually amount due to the volume of 1 liter).

If you really want to model "emptying of the bladder", you would need to go to MoBi and create respective events at wished time points.

@Tpa3

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Tpa3 commented Jan 31, 2019

Thanks for the input @HenrikCordes and @HenrikCordes ,

The reason I didn't initially go down that route was because the data I have was only taken on the last day of a TID multiweek study, and therefore I don't have data on the measure of the total amount removed into urine since the beginning of the study, and I don't know how much of the drug is still being removed into the urine from the previous application of the drug.

The somewhat inelegant solution I came up with was to run the simulation once for total amount in urine, note down the amount right before the final application of the drug and create an observer for the amount in urine minus the noted amount for right before the final application. This way I can still account for the drug being removed into the urine from the previous application of the drug and not have to have data on the total amount removed into the urine the weeks prior. It's not perfect since I have to run the somewhat large simulation twice each time I change a parameter to get a correct reading, but besides that I have seemed to have solved my own problem.

Thanks everyone!

@sfrechen

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sfrechen commented Feb 1, 2019

Well, in that case you need to go to MoBi anyway.
Hence, it would probably more elegant (and easier) to define an event to empty the urine compartment at the desired time point.

@Tpa3

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Tpa3 commented Feb 1, 2019

@sfrechen Thanks for the tip, that is definitely a far more elegant solution. The events BB is the one BB that I haven't totally understood yet, but this will be a wonderful opportunity to do so. I don't know when it changed but it looks like the help documentation for MoBi is a lot more detailed than before, so I'll take a look at that.

Thank you!

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