Hello, I have developed a joint parent-metabolite model for cyclophosphamide. I’ve run separate POPPK models for the parent and the metabolite (4-OH Cy) which were robust. I found a correlation between Kel (parent drug) and Kform (metabolite, but I use Ka symbol in my code), so I added a linear correlation. My issue is that I keep getting a point in my graph (-5.33, -5.33), which I can’t find in my data and I don’t know whether I set up my data sheet correctly, since I 've added BQL and MDV model #2. I also don’t know if because of this point I get high sd. Could you please help me by taking a look in my project? I would really appreciate your feedback. Thanks, Georgia P.S. I am trying to upload my project here and I can’t.
hi make sure that you select file to attach instead of select image to attach Samer
I know- I have been trying forever and no luck!
I think the file was too big. [file name=Metabolite_parent.phxproj size=8338717]Certara | Drug Development Solutions
Metabolite_parent.phxproj (7.95 MB)
I see you included the time zero and Concentration = 0 point. We cannot measure a concentration of exactly zero it is probably BQL why the BQL flag is not set to one for these observations ?
Dear Georgia There is also an error (in addition of Samer’s comment) also in your code fixef(dkadCL) = c(, 0.5, )) should be fixef(dkadCL = c(, 0.5, )) I am not sure it is related but the code in your project is definitively wrong. Strange it did not crash. Best Serge
Another code error ranef(diag(nVmet, nCLmet, nKa, dkadCL) = c(0.04,0.04, 0.04, 0.04)) should be ranef(diag(nVmet, nCLmet, nKa) = c(0.04,0.04, 0.04)) dkacl is a fixed effect not a random effect and you defined it through fixef statement. best Serge
Use foce els not foce lb. Best Serge
Can you try the following initial estimates tvVmet 4956390 tvCLmet 250934 tvKa 0.0621264 dkadCL 1.03951 stdev0 0.385595 Best Serge
When you have BQL you need to put 1 as you did in the column CObsBQl but the LOQ value in the response column.You put BQL which is not recognized by NLME. BEST SERGE
Not sure you got that but BQL in your data set in the response column should have the LOQ value (limit of quantification) and 1 (you did that) in CObsBQL column. Best Serge
Dear Georgia Please look at the site Box I have there a slightly different version of your model. Since you did not put the LOQ value I did the model without BQL. Once you have the LOQ value put it in the CObs column whenever CObs BQL is 1. Note that in your version once you have BQL you will not get the CWRES plots. Best Serge
Box That is the location
I have the LOQ value of the method is 0.0 ug/mL, but I didn’t know exactly how to incorporate that in the work sheet.
Also, don’t take into account the model with the covariates, model #2 is the one I was trying to run first and then I would add the covariates. Thanks, Georgia
Serge, I use for deriv(A1 = - (Ka* A1) fixed individual values of CL/V, which I have taken from the parent drug and I am trying to correlate with the metabolite.
Dear Georgia Can you give me the exact name of the model you are trying to use? I see 7 different models. Anyway I think that both Samer and my advises should enable you to successful analyze your data. Let us know if you still have trouble. Best Serge
Dear Serge, The joint model is #2. Thank you all for you comments and the support. I will try to improve my data sheet and make that model work. Georgia