Hello, I tried to simulate steady state with 3-day time/conc PK data available. Under the properties panel, I selected: Dosing type: Variable Repeat every 24 time units Output time range 0 to 216 (f.e., 9 days) I’m confused about the ‘Time’ values I need to add under the ‘Dosing’ Setup. I thought I need to add 0 - 24- 48 - 72 - 96 - 120 - 144 - 168 - 192 and 216 with the matching dose amounts, however, Phoenix WinNonlin would not execute showing the following error message “Dosing times are not consistent with the repeat values: Repeat 24 Max Time 216”? Wondering, what I do wrong here with adding repeat 24-hr time values as they are consistent with the repeat values that add up to 216? What, if I want to simulate different doses on different days since I chose ‘variable’ dosing? Shouldn’t I specifiy each 24 hrs-interval with its corresponding dose? I recently attended a Pharsight PK workshop in Mtn. View, where we would just add '0" in 6 rows, which I don’t understand? Hope, my question makes sense? Claudia
Hi Claudia, It sounds like you are using the NonParametric Simulation object. If you choose “Repeat every 24 time units” you are repeating the times you put in the Dosing set up. So if you only want three doses per day you should enter doses at 0, 8 and 16 hours. If you enter a dose time greater than 24 then you indeed will get the message; “Dosing times are not consistent with the repeat values: Repeat 24 Max Time 216”? If you want to simulate different doses on different days then do NOT choose “Repeat”, simply specify each dose amount and time explicitly; 
Does that help ? I’ve attached the file too to save you some typing, you can change my some what random dosing amounts to whatever you want. Best regards, Simon. ___________________________________ Forthcoming meetings and training -Certara | Drug Development Solutions; Introduction to WNL v5.x IVIVC: 6 Sept 2010, Amsterdam, Holland. **NEW course added ** Introduction to Phoenix v6.1: 7-9 Sept 2010, Amsterdam, Holland. Transitioning to Phoenix v6.1: 2 Nov 2010 Bristol, UK (prior to PKUK). Population analysis with Phoenix v6.1 NLME : 2-4 Nov 2010, Paris, France. Introduction to Phoenix v6.1: 8-10 Dec 2010, Paris, France. [file name=NPS_variable_Dosing_every_8h_to_216.xls size=18432]Certara | Drug Development Solutions (18 KB)
Thanks Simon, your response is what I needed! 
Claudia
Hi Simon & Claudia! A little addition. If your concentrations are the original measured ones (i.e., not log-transformed) in the Options-Tab the “Method for computation” should be set to Log rather than Linear as in Simon’s Screenshot. If you want see profiles matching your single dose profile change the “Number of data outpoint points” as follows: Your last dose is administered at 216 hours and you will be measuring the profile from 216-240 hours. The “Output time range” should be set to 0-240 hours if you want to see the saturation phase and the steady state profile, or to 216-240 hours for the last profile only. “Number of data output points”: Find the smallest time interval (in hours) of your single dose profile, divide 24 by this value, multiply by the number of profiles and add 1. Example: smallest interval 0.25 hours → 96 data points / day → 960 data points / 10 days + 1 = 961 data points. If you use any other number of data points, you will end up with interpolated values which will not match the single dose profile.
Helmut, Thank you very much for your valuable addition to my question. I just corrected my data according to your suggestions. For example, I entered ‘481’ as ‘Number of data output points’ as my smallest time interval was 0.5 hr. As I simulated steady state from 0 to 240 hrs (9 days) with repeated dose administration every 24 hrs, I ended up with 10 time profiles plus 1 = 481? Just want to make sure that I did enter the correct value since I was confused what you meant by ‘number of profiles’ (=10?) Thanks again, I didn’t know about it. I was told to simply play around with the ‘Number of data output points’ or chose at least a number above 100. Claudia
Hi Claudia! [quote][…] I entered ‘481’ as ‘Number of data output points’ as my smallest time interval was 0.5 hr. As I simulated steady state from 0 to 240 hrs (9 days) with repeated dose administration every 24 hrs, I ended up with 10 time profiles plus 1 = 481?[/quote] Yes, I think that’s correct. Have a look at the Output Data, Concentrations-Sheet. I guess that with 481 data points you get every 0.5 hours in the time column. You can try it with 480; I assume the time intervals will be 0.5010417 hours then. [quote]Just want to make sure that I did enter the correct value since I was confused what you meant by ‘number of profiles’ (=10?)[/quote] Sorry, was confusing. You will dose for nine days, but the 9th profile ends at 240h (at day 10)…