I’m trying to IV model PK data from a cross-over study, where there is still residual drug concentration in the first samples from the previous study (PO administration). My approach has been to model the IV data as steady-state in Phoenix 6.3 (NMLE, Naïve pooled) to enable fit to the ‘pre-IV’-dose. I have tried using dose time as 0 or 0.001 h in the data sheet. In the first case, Phoenix successfully fits to data > 0 h, but predicted conc for the ‘pre-dose’ (0 h) are all way too high. In the latter case, all predicted conc at time 0 is 0. The approach has work successfully for modelling of PO data (dose at time 0). Any suggestions how to model these IV data? Best regards, Mads [file name=IV_SS___Pharsight.phxproj size=744582]/extranet/media/kunena/attachments/legacy/files/IV_SS___Pharsight.phxproj[/file]IV_SS___Pharsight.phxproj (727 KB)
Mads, I think the problem may be because your data isn’t really at steady-state in this second period if it’s carry-over? Have you tried to model both doses in one model with a time continuous from the first dose? there is an example of graphically building a simultaneous IV and ORal dosing model in the NLME examples guide. (you won’t necessarily need an NLME license for that to work.) Simon.
Thanks the suggestions, Simon. I’ll try a sequential approach. Alternatively, I discovered that using a short 30 s infusion instead of IV bolus as route of administration solves the fitting issue to the first data point. Best regards, Mads