I'm one of your Canadian clients
our office is in Montreal.
In terms of this project, you are correct, I'm modeling a single-dose subQ macromolecule injection. We know that there is lymphatic uptake of proteins however my data clearly suggests a pseudo-zero order input and I've got a very intenstive sampling regimen to characterize this input. This is followed by a more linear increase in slope. This cannot be modeled with simply a first order ka or even 2 first order ka's split between the central and absorption compartment. Hence my proposal to allow a fraction to input directly into the lymph and a fraction via first order into the vasculature.
There is some basis for this approach from PBPK models and I am attempting to use the NLME program to characterize this approach.
For the point about the covariate, can you elaborate why we would put this covariate in?
when you state "in the dataset" what goes in the dataset? I'm not sure I understand this part. although I can understand why dose itself could be a covariate. Are we simply stating that dose is a covariate so it maps the dose and dose time and knows there is only a single-dose administered?
Incidentally, and not related to my original question, but I know from your Webex's you are a quite the wizard with these things.
What in your opinion is the best way of calculating total Clearance when you have CL from the central compartment and the target mediated clearance which includes a rate of internalization of the receptor-protein complex?
Any help here would also be appreciated
תודה
Elliot