What is clinically relevant? [Design Issues]

posted by bebac_fan – US, 2018-04-06 22:53 (2295 d 23:53 ago) – Posting: # 18648
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Dear Helmut:

I believe the spaghetti plots you posted are actually indicative of a infusion of unbound drug.

Release of the encapsulated form follows first order kinetics and is Sequential - kind of like metabolic clearance from parent --> metabolite.

Luckily, you also posted the parent/metabolite curve for doxorubinol. Because of similarity in process, if no free drug is infused, bound and unbound PK should follow the same general shape we see in parent + metabolite.

The fact that total + free dox concentrations are colinear is pretty strong evidence for co-infusion of bound + unbound. Further, the fact that there isn't a lag time in unbound, as well as a nonlinear shape, is evidence, too.

Thanks,
BF

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