Double peak PK profile for deconvolution.

How to do the deconvolution if the PK profile presenting a double peak? Any ideas?

Coco - can you give us some idea of the extent and timing of the second peak - do you know the cause ? perhaps an example profile would help guide our suggestions Simon.

Hi Simon! Sorry for the late response! I’ve attached the project file to the forum. It could noticed from the xy plot that the most of the in-vivo profile presented a double peak phenomenon. I’m not sure about the cause. Another problem is that the reference for deconvolution is a IR oral dose and after deconvolution the fraction of absorption goes up to 200%. I’m not sure if this Fabs is right. Can you give me some advice to solve the problem. Thanks in advance! Coco [file name=New_Project.phxproj size=6679832] /extranet/media/kunena/attachments/legacy/files/New_Project.phxproj[/file]

New_Project.phxproj (6.37 MB)

Coco, I’ve looked at your plots and I see the double peak is present at different times - I guess there is some unevenness in how the extended release formulation is breaking up/releasing the drug double_peak.jpgFirstly are you sure that the IR dose was really 5mg - i.e. the same as all your controlled release formulations? Because if you perform a simple NCA on the raw profiles you will see you are getting less than half the AUC with the IR formulations AUC.jpgAnd if you look at the half-lives it is 2hours versus 15-20 for the extended release formulation overlayLz-20120229.jpgDo you think you sampled the IR profile long enough - is there perhaps a second phase of the ‘true’ elimination that occurs after your last timepoint of 10 hours e.g. it is really a 2compartment model?