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Time course of RO of agonist in the presence and absence of an antagonist


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#1 Kapilrp

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Posted 31 March 2020 - 09:18 PM

Seeking help in linking the following 

 

 

Time course of RO of agonist in the presence and absence of an antagonist by following steps.  
 

seeking help with step 3 simulation of time course of RP of an agonist A where agonist A and antagonist B plasma concentrations are declining with time:

 

  1. Simulate PK (c vs t) for A (agonist), 1 compt open model
  2. Simulate PK (c vs t) for B (antagonist), 1 compt open model
  3. Linking these two PK profiles to generate time course of RO below Receptor Occupancy, RO (on the left hand) where, where, Ki (X = 1.25 nM (affinity for agonist A) and Ki (Y = 5 nM) affinity, for antagonist B) are known

 

RO, when X and Y are fixed at 1.25 and 5 nM, respectively, A and B are agonist and antagonist concentrations from 1 & 2 above.

 

                      A

RO =  -----------------

              A + X (1 + B/Y)

 

Thank you very much!

Ram

203-321-9682



#2 Simon Davis

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Posted 01 April 2020 - 02:15 PM

Hi Ram, It would b enice to see how far you've got so far with your project/PML and then people can guide you further, thanks.   Eg. construct a data set that maybe gives an indication of the conc ranges you want to simulate over.  Simon.



#3 Kapilrp

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Posted 01 April 2020 - 09:32 PM

Hi Ram, It would b enice to see how far you've got so far with your project/PML and then people can guide you further, thanks.   Eg. construct a data set that maybe gives an indication of the conc ranges you want to simulate over.  Simon.

 

Thank you very much Simon for the heads up.

 

Please find attached Project with the PK simulations. 

 

Please find attached Phoenix Project with PK simulations of agonist (A) and antagonist (B)

 

The respective equilibrium dissociation constants, Kd (X below) are 1.25 nM (or 0.5 ng/mL) for Agonist A and Kd (Y below) 5 nM (or 2.5 ng/mL) for antagonist B. 

 

I wish to link these two simulated concentrations (ng/mL),  one for agonist and one for antagonist to the following expression to solve for time course of RO as our first step for flexibility in projecting simulations in Phoenix (as opposed to a lot of cutting and pasting in Excel). 

 

Thank you very much for everyone's kind help!  Please stay safe everyone!Attached File  Agonist Antagonist RO v1.phxproj   581.54KB   50 downloads

 

 

                     A

RO =  ------------------------

            A + X ( 1 + B / Y)






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