Hi, I posted this originally in the modeling and simulation thread but seeing its specific to understanding how to use the NLME function I’m reposting here…also it seems the NLME thread is monitoring more frequently. I have both repeat dosing and single dosing (different animals) in the same file. I am not seeing the doses being fit and the predicted plots (eg popDV, IPRED vs IVAR) make it seem like a straight line is being fit across all the trough values leading up to the full profile in the repeat dose group. I saw a separate post where Serge posted a model with single and repeat dosing and the predictive plots had clear profiles fitted for each dose so I’m concerned I’m not accounting fo the repeat dosing in the model Can someone look at this model attached to confirm its being set up correctly? thanks Elliot File Attachment
Dear Elliot There is no file attached. Can you please try again to attach the file. Best Serge
hopefully this works [file name=Cyno_SC-20140222.phxproj size=702663]Certara | Drug Development Solutions (686 KB)
Dear Elliott Please see attached a corrected version of your model. First I saw that the IV dose was empty and therefore I mapped the SC1 and SC2 doses by adding one absorption compartment. The true is that there is not enough information to estimate the fraction and therefore the estimate of 50% initial stays like that (tvF1=0 means 50% fraction). Anyway to show you that the doses are indeed taken into account I added a table. What is happening is that if you just connect the predicted responses at the observed time you will not see the accumulation and it seems like a single dose but in fact there is accumulation and you can see from the table I generated. Then all is good and I do not see special issues other than that there is no need for multiple absorption here. If you want just one mapped dose, then your model is OK but no need to even define F1. best Serge [file name=Cyno_SC-20140222-2.phxproj size=1457806]Certara | Drug Development Solutions (1.39 MB)
Dear Elliott I updated the project to include vpc for each strata (single and multiple). It can be found at the following online site Box Now the idea was to add a column called singleormultiple and to each patient say if it was a single or multiple. then rather than to use the ALLPCdata as output, you create a simulated table with many time points (0 to 332 II think) by interval of 1 and ask for 100 replicates. Now I manually took the vpc output and put single or multiple in the singleormultiple column. You could do it with the program if you use 0 and 1 for single and multiple for example. Anyway then you do a descriptive statistics and ask for confidence intervals. Then oyu merge the des stat output with your original data (that have also singleormultiple column). Note that I changed Time to time to match time in the des stat. After merging, then you just plot and get beautiful VPC’S. Hope it helps. best Serge [file name=vpc_for_plots.xls size=95744]Certara | Drug Development Solutions (93.5 KB)
Thansk Serge! This is similar to what I did but I am glad you confirmed the approach. I was really confused when it looked like a straight line was being drawn for the repeat dose predicted PK. Just to note for the record, I had previously fit IV data and fixed the systemic parameters. it turns out (at least using NLME) that a multiple absorption route is a better fit than a single path. anyway, that was why I originally had the IV in the dataset…but I had split it off for the purposes of attaching the project. Thanks Elliot