Re: AUC Calculation in Simulation with and without EST

Title: Paul R Many thanks to Mats, Nele, and Joachim for their guidance. Nele's suggestion to use $DES to calculate AUC mirror's Joga's suggestion for this in the past, but has the interesting twist of closing additions to it after 24 hours. I did not think this the best approach (vs F1*AMT/CL) in my case because each mouse had so few samples. With respect to Mats' suggestion to use $SIM + $EST without POSTHOC, I noted that there is not a difference in my output TABLE if it is left in the $EST line (but then my MAXEVAL was =9999. When I changed to $SIM + $EST MAXEVAL=0, the AUC was different than my trapezoidal, as below: $SIM $EST MaxEval PostHoc CL F1*AMT/CL AUCtrapezoid VarETACL YES NO N/A N/A 0.464 0.531 1.68 1.15 YES YES 9999 YES 0.838 0.480 0.482 0.00 YES YES 9999 NO 0.838 0.480 0.482 0.00 YES YES 0 YES 0.443 0.556 1.68 1.1 YES YES 0 NO 0.443 0.556 1.68 1.1 [Initial estimates for the above are CL=0.147, F1=0.405, AMT=0.608, $OMEGA .238 SO AUC = 1.68] My mistake it seems was to have left METHOD=1 (FOCE) in the $EST term. That (I think) is why the presence or absence of POSTHOC had no effect and confused me. And it is why I obtained new estimates of CL and thus the integrated (F1*AMT/CL) AUC. My understanding is that the varETAs are 0 because I only simulated one, hypothetical individual. When I corrected $EST to the FO method, I obtained the following for an N=1 $SIM & $EST: $SIM $EST MaxEval PostHoc CL F1*AMT/CL AUCtrapezoid VarETACL YES YES 0 NO 0.147 1.68 1.68 0 YES YES 0 YES 0.373 0.659 1.68 0.932 So now I have my plot of the mean concentrations for this dose and route (from PRED column), I will remember to check the FO/FOCE toggle in $EST, and I apologize for bothering everyone with problems arising from my late-night coding error. Paul -- Paul R. Hutson, Pharm.D. Associate Professor UW School of Pharmacy 777 Highland Avenue Madison WI 53705-2222 Tel 608.263.2496 Fax 608.265.5421 Pager 608.265.7000, p7856