fit data from two different doses simultaneously

Phoenix Certara Forums Phoenix WNL basics
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Hi, I am trying to fit the data from two different doses simultaneously to determine whether a single combination of values for CL and V will describe the drug’s disposition (after iv bolus) in order to assess PK linearity. I am using classical PK modeling, but I just can’t get any results-I think I don’t arrange my data correctly. Can anyone give me some advice? Thanks, Georgia

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Georgia - if you can attach your PHXPROJ or at least your data file then we have a much better chance of commenting if your data structure/mappings need to be changed. Simon

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Here is my excel file, Thanks, Georgia

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OK Georgia, I’m attaching your file with a couple of suggestions but also some questions; 1) am I right to guess Dose1 is IV bolus (i.e. admin <1min duration?? and Dose 2 is also a second IV dose? or do you have different routes too? 2) the dose events should be on the time line that they occurred - I assume that dose 1 happened at time 0; however when was the second dose? a) line 8 the column ‘dose’ changes at 478 min, is that correct? b) at line 9 the time has gone back to 16.2 min, so what is the Total time elapsed since the first dose? c) line 8, 478min from the graph looks like it should be associated with dose event 1. [file name=_5_data_all.xls size=24576]Certara | Drug Development Solutions If, as I am guessing you redosed at 480 minutes then I think you might have a data file like the ‘suggestions sheet’ Simon PS which gives me this fit _5_data_all.xls (24 KB)

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Well, the issue is that these two data sets are independent. They were administered to a rat independently, but I need to run them in the same model and show the PK linearity. The second dose was given at t=0. You are correct, t=480 min is dose 1 and then I have data for dose #2 at 16.2 min. Thanks, Georgia

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Hi Georgia, If you run it as Naïve pool Phoenix model, but with population checked so you can use your Dose Event as ID and the two are fit simultaneously to give; Parameter Estimate Units Stderr CV% 2.5% CI 97.5% CI Var. Inf. factor tvV 812.612 mL/kg 0.2597 0.0312 812.05 813.17 32.593 tvCl 4.7709 0.00183 0.0384 4.7669 4.7748568 0.0028476 is that what you wanted? Simon [file name=georgia63.phxproj size=736799]Certara | Drug Development Solutions (720 KB)