Hi, I could use some assistance with the following. I obtained PK parameters from a popPK model and I am conducting Individual Sim to explore different dosing strategies. The PK parameters are manually entered and frozen in Fixed Effects. The endpoint of interest is the T-high so I am bringing the Sim data sets for different doses back in to NCA. The original data is derived from 500mg q6h dosing, and when I Sim a 1000mg q6h dose the T-high is the same despite higher simulated plasma concentrations. Logic and experience tells me that if you double the dose and have higher concentrations, the T-high should be different than for the lower dose. In addition, NCA of the sim data shows different Vd and CL than what was specified in the sim conditions so I am suspicious that something is amiss… shouldn’t it be identical to what I specified to generate the sim data? I appreciate the expert review of my issue. Thanks. kevin [file name=PhxProject.phxproj size=891011]Certara | Drug Development Solutions (870 KB)
Kevin, I’m honestly not sure what you’ve done to get these different simulations, are you trying to look at values at SS or after a single dose? do you want simulate as bolus or infusion in the NCA you are using to evaluate the therapeutic upper range is 16 for all profiles except in NCA of Sim 1000mg q6h where it is 1, 2, 4, 8, 16. the ? original NCA, 500mg q6h has no therapeutic ranges but the doses have different subject numbers to the worksheet mapped to conc. I suspect it would be easier to follow what you had done if you had kept each simulation object. Please can you double check your file and perhaps re-post with some clarifying notes. Simon. 
