Calculating Simulation PK Parameters for 3 compartment model

[emily]

Dear all,

Our drug was administered by constant rate IV infusion in dose 72mg/m^2, Q4W and would like to konw the simulation profile and PK parameters change with 36mg/m^2, Q2W dosing regimen, especiallly for two analytes (C and C3 in attached file). I have some following questions:

1. Are the analytes of C and C3 simulation results able to be generated at the same time ?

2. How can I generate the secondary PK parameters (e.g. Cmax, AUClast, MRT) wih these two analytes in two dosing regimen 72mg/m^2, Q4W and 36mg/m^2, Q2W, respectively ?

Thank you very much.

Emily

[SimonDavis]

Emily, there is no file attached but if you email it to me (simon.davis@certara.com) I can attach it for you.

But yes it absolutely should be possible to see all analytes at the same time, just request them in your table.

Regarding secondary parameter the exact code would depend on your model but the syntax is;

secondary(Ke = tvCl/tvV)

you can get many written for you if you use the “set WNL model” button on the Structure tab before going to graphical or textual mode. https://support.certara.com/forums/topic/192-integration-for-auc-in-pml-model/?p=612

Simon.

AUC and some others you can also derive and then request in a table, see https://support.certara.com/forums/topic/371-assistance-calculating-auc-as-secondary-parameter/?p=1639

PS EDIT, project attached with example of requesting an additional table for the C3, C4 and C5 concentrations.

emily3com_2analyte_sim20221019.phxproj (624 KB)

[linh.nguyen]

Hi,

I am trying to use a 2 compartments PK IV infusion model with michaelis menten but I don’t see this in the models library. can you help where i can find this?

Thanks,

Linh

[SimonDavis]

Hi Linh, the option I think you are looking for is the check box; “saturang?” under clearance.

Clearance: Model is expressed as differential equations having clearances associated with a compartmental model. Adds the inter-compartmental clearance parameters, such as Cl, the clearance rate. If Clearance is selected, the Saturating checkbox becomes available. Check the Saturating checkbox to convert the model to a saturable elimination (Michaelis-Menten kinetics) model. A saturable model uses two parameters:
Km: Concentration to achieve half of maximal metabolic rate.
Vmax: The maximum metabolic rate.
from https://onlinehelp.certara.com/phoenix/8.3/index.html#t=topics%25252FPK_model_options.htm

Note some simple examples can also be created using the “set WNL model” option.

Simon.