Bioequivalence and Bioavailability Forum • What is clinically relevant?

What is clinically relevant? [Design Issues]

posted by bebac_fan – US, 2018-04-06 22:53 (2004 d 17:11 ago) – Posting: # 18648
Views: 5,147

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

Complete thread:

Counterintuitive? nobody 2018-04-03 11:16 [Design Issues]
- 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
  - 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