What is clinically relevant? [Design Issues]

posted by Helmut Homepage – Vienna, Austria, 2018-04-07 00:05 (2004 d 17:07 ago) – Posting: # 18649
Views: 5,162

Hi BF,

❝ 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.

Did you notice the different concentrations scales (encapsulated doxorubicin: µg/mL, free: ng/mL)? On the average free is less than 1% of encapsulated. With just three sampling times during infusion I would say it is not possible to separate zero order (encapsulated) from first order (release from the liposomes).

❝ 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.

What do you mean by bound + unbound? Encapsulated and free?

❝ The fact that total + free dox concentrations are colinear is pretty strong evidence for co-infusion of bound + unbound.

I still don’t think so. The release can be quite quick. Hence, the shapes looks similar but the concentrations of free doxo are always pretty low compared to encapsulated doxo.

❝ Further, the fact that there isn't a lag time in unbound, as well as a nonlinear shape, is evidence, too.

Again, I would contradict that. I don’t expect a lag-time. I would rather say that doxo follows Le Chatelier’s principle and is simply driven out from the liposomes due to the concentration gradient (Cliposomes > Cblood).

Dif-tor heh smusma 🖖🏼 Довге життя Україна! [image]
Helmut Schütz

The quality of responses received is directly proportional to the quality of the question asked. 🚮
Science Quotes

Complete thread:

UA Flag
 Admin contact
22,764 posts in 4,776 threads, 1,628 registered users;
24 visitors (0 registered, 24 guests [including 9 identified bots]).
Forum time: 17:12 CEST (Europe/Vienna)

The object of statistics is information.
The objective of statistics is the understanding of information
contained in data.    Irwin and Marylees Miller

The Bioequivalence and Bioavailability Forum is hosted by
BEBAC Ing. Helmut Schütz