Hi Am I right in thinking that when carrying out a deconvolution analysis on an oral PK profile in WinNonlin, the input function generated tells you the rate and extent of not just absorption (transfer from gut lumen into enterocyte) but also includes first pass metabolism in both intestine and liver - so that the ‘absorption rate’ includes metabolism rates as well, and the final cumulative ‘absorption’ is in fact the bioavailability, and not Fabs??? Is this different in the IVIVC toolkit? (I haven’t got access to this yet) Thanks Kathryn
Yes, you are correct in the case where the UIR (unit impulse response function) represents a response to an IV bolus. If the UIR includes absorption kinetics, then the deconvolved input actually represents in vivo dissolution. You could think of the deconvolved input as referring to the rate/extent of introduction of drug to the dosing site of the UIR. It is the same in the IVIVC toolkit. If you want to somehow separate the various first pass mechanisms, you will need more than just plasma data. If you already know the metabolic rates in gut and liver, and have urine or fecal data, you could post-process the deconvolution output to compute specific contributions. I hope this is helpful. Cheers, -Jason