Re: [NMusers] AUC Calculation in Simulation with and without EST

[Paul Hutson]

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