I would like to perform some PK/PD simulations either as a direct or link model. What I want to do is to fix both PK and PD parameters and then simulate different doses and get resultant PK and PD profiles. So far, even with the great advice from Pharsight support, I have not been able to perform this function. Is it possible to do this without first having to fit the PK/PD? regards Brian
Brian, which part(s) are holding you up? I saw that you have final parameter estimates from some previous modelling, you know the model you want to use and you have switched it “simulation” mode. the two remaining things you need to supply WNL with are the sampling schedule e.,g. an “x” column of time 0 0.5 1 2 4 8 12 24 36… and the dosing schedule(s), e.g. 0 20 12 10 24 10 36 10 if you have more than one design/ profile then you will need to ensure they are identified as by mapping to SORT e.g. regimen if you can please attach the project you’re having problems with and then we can identify what step /option has been missed. the attached example shows 4 different dosing regimens once, twice and three times daily dosing, to illustrate VIF in assessing sampling designs for a simple PK model, but the same principle would hold for PK/PD. Simon. [file name=Ex_17_sim_mult.phxproj size=313832]Certara | Drug Development Solutions (306 KB)
Simon Thanks for the response. Not sure what is happening. When you say “attach the project” do you mean the assembled project in Phoenix or the data to assemble the project. regards Brian
Brian, the"assembled project in Phoenix" please, i.e. “File | Save Project as” xxxx.PHXPROJ as I did above. then we can see what settings are correct and what have been omitted or need some tweaking. Simon.
project attached. I managed to run the simulation this morning but didn’t get the response I wanted. It set initial values of the PD parameters to zero and then didn’t change them. regards Brian [file name=simulations.phxproj size=506201]Certara | Drug Development Solutions (494 KB)
Brian the initial parameters which were set to zero were due to a mismatch in parameter names ( a Phoenix model can support re-mapping these) 
in this case the quickest way to get the output I think you were looking for was just to type the info in to an “internal worksheet” as I’ve illustrated in the attached, I also named the worksheets to make it clear to track what was being mapped where. 
Alternatively in this case we could have just re-named the parameters either in the original worksheet or using a “Column Properties” workflow object. Simon. [file name=simulations-20110711.phxproj size=703067]Certara | Drug Development Solutions 
Simon Thanks for this. It seems that it was as simple as unit names not matching. I will look at what you produced for me but the graph doesn’t look exactly how I wanted it. I was looking to have 4 bolus IV injections with a 6 minute gap between them. The PD response should have returned to baseline between the injections - probably another case of me not inputting the data correctly. kind regards brian
Simon another quick question. How do I open the project that you sent. It is a Zip file which is easy to open but it gives me a folder containing loads of files and a file I cannot open because it is password protected. Brian
Simon Thanks for this. It seems that it was as simple as unit names not matching. I will look at what you produced for me but the graph doesn’t look exactly how I wanted it. I was looking to have 4 bolus IV injections with a 6 minute gap between them. The PD response should have returned to baseline between the injections - probably another case of me not inputting the data correctly. another quick question. How do I open the project that you sent. It is a Zip file which is easy to open but it gives me a folder containing loads of files and a file I cannot open because it is password protected. Brian
I guess you’re using IE, this is a known issue as a browser - if you rename the zip as a PHXPROJ then it will work fine. (Firefox doesn’t seem to have this problem). Simon.
Simon The Zip file tells me that it is password protected Brian