# Covariates and Exposures (AUC & Cmax) **URL:** \ **Category:** Modelling and Simulation\ **Created:** [June 15, 2016, 7:09am UTC](https://forum.certara.com/t/covariates-and-exposures-auc-38-cmax/2983 "2016-06-15T07:09:09Z")\ **Posts on this page:** 2\ **Page:** 1
**Author:** ![raghavchowdary](https://avatars.discourse-cdn.com/v4/letter/r/b782af/32.png) [@raghavchowdary](https://forum.certara.com/u/raghavchowdary)\ **Post date:** [June 15, 2016, 7:09am UTC](https://forum.certara.com/t/covariates-and-exposures-auc-38-cmax/2983/1 "2016-06-15T07:09:09Z")
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 ---
**Author:** ![SimonDavis](https://avatars.discourse-cdn.com/v4/letter/s/d9b06d/32.png) [@SimonDavis](https://forum.certara.com/u/SimonDavis)\ **Post date:** [June 15, 2016, 10:04am UTC](https://forum.certara.com/t/covariates-and-exposures-auc-38-cmax/2983/2 "2016-06-15T10:04:27Z")
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,