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:
Simulate PK (c vs t) for A (agonist), 1 compt open model
Simulate PK (c vs t) for B (antagonist), 1 compt open model
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.
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.
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).