Covariates and Exposures (AUC & Cmax)

Phoenix Certara Forums Modelling and Simulation
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Dear All,

I have modeled the PK data of a compound and found that the covariates, weight (on V1 and V2 , model is 2 compartment) and creatinine clearance (on Clearance) have significant effect (decrease in OFV and other model diagnostics).

I have few questions on the simulation of exposures.

How do i simulate the exposures (AUC & Cmax) in subjects with low creatinine clearance, for e.g the average creatinine clearance in males and females is ~ 6.5 - 8 L/h with normal kidney function and as age increases the creatinine clearance decreases and the exposures may increase. How do i simulate the exposures in subjects with decrease renal function ?

Where do i find or how to get the individual estimates of clearance and volume of distribution and Ka ? do i have to use the table option for the same ?

Any help is appreciated.

Best regards,

Raghav

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Raghav, the individual estimates (post hocs in NONMEM I think) are the THETA + ETA.

To simulate a population with impaired clearance you can adjust the Clearance parameter by that factor, maybe someone has a worked example they can share; I can’t recall if I have one and I’m a bit busy this week.

Simon,