Log in
RegisterWhat is clinically relevant? [Design Issues]
posted by Helmut 
– Vienna, Austria, 2018-04-06 22:05 (1593 d 20:22 ago) – Posting: # 18649
Views: 4,984
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).
» 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 🖖![[image]](https://static.bebac.at/pics/Blue_and_yellow_ribbon_UA.png)
Helmut Schütz
![[image]](https://static.bebac.at/img/CC by.png)
The quality of responses received is directly proportional to the quality of the question asked. 🚮
Science Quotes
Dif-tor heh smusma 🖖
Helmut Schütz
The quality of responses received is directly proportional to the quality of the question asked. 🚮
Science Quotes
Complete thread:
- Counterintuitive? nobody 2018-04-03 11:16 [Design Issues]
![[Mix]](https://static.bebac.at/img/mix.png "open in Mix view")
- Counterintuitive? bebac_fan 2018-04-03 18:20
- Counterintuitive? nobody 2018-04-03 23:25
- Counterintuitive? bebac_fan 2018-04-04 00:43
- Counterintuitive? nobody 2018-04-04 11:03
- Counterintuitive? bebac_fan 2018-04-04 00:43
- What is clinically relevant? Helmut 2018-04-04 16:49
- What is clinically relevant? nobody 2018-04-05 10:04
- What is clinically relevant? bebac_fan 2018-04-05 14:19
- What is clinically relevant? nobody 2018-04-06 09:22
- What is clinically relevant? Helmut 2018-04-06 16:10
- What is clinically relevant? bebac_fan 2018-04-06 20:53
- What is clinically relevant?Helmut 2018-04-06 22:05
- Korsmeyer–Peppas’ model mittyri 2018-04-06 23:36
- What is clinically relevant?Helmut 2018-04-06 22:05
- What is clinically relevant? bebac_fan 2018-04-06 20:53
- Counterintuitive? nobody 2018-04-03 23:25
- Counterintuitive? bebac_fan 2018-04-03 18:20
Ing. Helmut Schütz