I have developed a pharmacodynamic interaction model of two anti-hypertensive drugs through turn over driven models. I want extrpolate my model to clinical data. Can anyone suggest me the ways to do it.
I have deloped the model for single dose data in preclinical data but the reported data in clinical pharmacodynamic data is available in repeated dose. How to extrapolate preclinical pharmacodynamic interaction model to clinical model.
Not sure if this is still of interest to you but my question back to you would be, is your pharmacodynamic model in preclinical species linked to some exposure of the drug i.e. concentration? or just dose?
if its linked to PK concentratios, I would advise considering scaling up your PK. Assuming the pharmacodynamic response is in a relevant animal model, your base assumption could be the PD response is directly scaled from animals to humans, however it will be the concentrations which will change between preclinical and human species.
if its dose vs PD response, I would be very skeptical of the ability to scale this response to humans.
If you have any questions on scaling to human from animal, I’m happy to help.
Elliot
I sincerely thank you for reply. Yes, I had established the time-concentration-response model using PK/PD indirect response model in Spontaneously Hypertensive rats. Now I want to extrapolate model parameters Kin, K out, IC50, I max, SC50 and S max to humans. With these scaled parameters could it be feasible simulate the response in human data with PK parameters and therapeutic dose known in them . If so how to simulate the time versus response data in humans. Kindly suggest me.