Diff. between NCA and PK model for IP study

Hello everyone, I have performed intraperitoneal (IP) pharmacokinetic study in mice. The data is as follows: Time (h) Conc_ (ug/L) 0.5 267333.33 0.75 90433.333 1 44866.667 2 5493.3333 8 163.66667 12 140 24 80.8 Using Phoenix Winnolin, I did NCA with Dosing Type : IV bolus ( assumed bioavailability equal to one) with Linear Trapezoidal and Linear Interpolation and got AUCINF_OBS 758404.86. I have also tried other calculation methods like Linear Trapezoidal Linear/Log Interpolation, Linear up log down, but all the methods resulted in similar values. In addition to this, I also performed WNL 5 Classic PK model no. 7 and obtained AUC =293061.38 (less than half of value obtained in NCA). The weighing scheme used: 1/(yhat*yhat). Based on the above context my queries are: 1. Why the values obtained by both the methods (NCA and WNL 5 Classic model) are so different? Any comments will be greatly appreciated. Thanks and regards, Chetan [file name=QA_pharsight_IP.phxproj size=374644]Certara | Drug Development Solutions (366 KB)

Chetan, I thnk the clue is in the AUC_%Back_Ext_obs at 85.821299 % NCA just back extrapolates the first two points and is giving a much higher estimate of Czero 2336158 versus the Fitted value which is less than a third of that; 724848 So that’'s the main source of your extra AUC; as indicated by the first shaded area in the image below; Remember it’s a log scale so that’s a large area. Simon.