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Modeling for transgene product production

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#1 gchan@regenxbio.com



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Posted 18 December 2020 - 07:52 PM



After attending the modeling introduction course and going through the phoenix assistance, I cannot locate the function within max likelihood model to allow using a rate of transgene product production for the point of dosing. The point of dose can be in the central or peripheral compartment. The most relevant area that I find is related to setting "infusion possible" and applying a rate, which I am not entirely sure how phoenix would recognize the unit (dose mg? / time hr? day? min?). If you can point me in the right direction, it would be much appreciated. 


Essentially I am interested to model the PK of a transgene product, which is produced by an organ, lets say in the kidney, at a constant rate or a rate that can be describe by a math equation related to time. The transgene product or aka the test article is considered going right into the central compartment obviously via intravascular route, and there is no external dosing. Thatsit the drug is produced within your body. Therefore the traditional absorption compartment or point of IV dosing into the central compartment do not capture our product.


Many times.



#2 kniefort



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Posted 21 December 2020 - 04:15 PM

Hi Gary,


You can do this with a command line model.  Below is an example of a 2 cmpt model with a constant rate input into compartment A1:



                deriv(A1 = - (Cl * C)- (Cl2 * (C - C2)) + 3)   # here, 3 is the constant input into A1 from e.g., kidney

                deriv(A2 = (Cl2 * (C - C2)))

              C = A1 / V

                C2 = A2 / V2

                error(CEps = 0.1)

                observe(CObs = C * (1 + CEps))

              stparm(V = tvV * exp(nV))

                stparm(Cl = tvCl * exp(nCl))

                stparm(V2 = tvV2 * exp(nV2))

                stparm(Cl2 = tvCl2 * exp(nCl2))

                fixef(tvV = c(, 12, ))

                fixef(tvCl = c(, 4, ))

                fixef(tvV2 = c(, 58, ))

                fixef(tvCl2 = c(, 7, ))

                ranef(diag(nV, nCl, nV2, nCl2) = c(1, 1, 1, 1))



The above assumes that the endogenous compound starts with a value of 0 at time 0, which may or may not be what you want.  If you can share the model you have so far it would be helpful for us to be able to give more specific feedback.  


Best Regards,



Edited by kniefort, 21 December 2020 - 04:15 PM.

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