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RegisterSynovia is a nasty beast [Dissolution / BCS / IVIVC]
Hi Helmut,
Oh Gush! Loss of lubrication is the one of the components of diseases causing arthroplasty.
Citing the original article:
The lack of agreement between observed data and model predictions on diclofenac amounts in the presumed site of action, the synovial fluid, even after model refinement can be attributed to the differences in physiology between the muscle and the synovial fluid; the muscle compartment was modified to mimic the synovial fluid only in terms of its volume without changes in the physiology. For instance, protein expression, diclofenac partitioning and diffusion, and extent of vascularization may be some of the differences between the muscle and the synovial fluid physiology and its interplay with diclofenac that were not taken into account. Finally, a suboptimal model performance may be attributed to not accounting for the disease (osteoarthritis) pathophysiology—namely, the increase in the synovial fluid volume and local blood flow commonly reported in patients with knee osteoarthritis due to inflammation; model predictions generated in virtual healthy volunteers were compared with observed data collected in patients.
Figure 3e:
![[image]](img/uploaded/image789.png)
hmmm... Suboptimal?
When you worked hard and the experts were involved, some fails could be named just as suboptimal results
❝ Turned out that >50% had a so-called ‘dry knee’, i.e., no synovia at all.
Oh Gush! Loss of lubrication is the one of the components of diseases causing arthroplasty.
❝ Given all that, I’m asking myself on which data the FDA’s model is based upon and how reliable they are. 
Citing the original article:
The lack of agreement between observed data and model predictions on diclofenac amounts in the presumed site of action, the synovial fluid, even after model refinement can be attributed to the differences in physiology between the muscle and the synovial fluid; the muscle compartment was modified to mimic the synovial fluid only in terms of its volume without changes in the physiology. For instance, protein expression, diclofenac partitioning and diffusion, and extent of vascularization may be some of the differences between the muscle and the synovial fluid physiology and its interplay with diclofenac that were not taken into account. Finally, a suboptimal model performance may be attributed to not accounting for the disease (osteoarthritis) pathophysiology—namely, the increase in the synovial fluid volume and local blood flow commonly reported in patients with knee osteoarthritis due to inflammation; model predictions generated in virtual healthy volunteers were compared with observed data collected in patients.
Figure 3e:
hmmm... Suboptimal?
When you worked hard and the experts were involved, some fails could be named just as suboptimal results
—
Kind regards,
Mittyri
Kind regards,
Mittyri
Complete thread:
- Virtual Bioequivalence: a myth or coming reality? mittyri 2018-06-09 22:39
![[Mix]](https://static.bebac.at/img/mix.png "open in Mix view")
- Virtual Bioequivalence: a myth or coming reality? jag009 2018-06-13 02:40
- Virtual Bioequivalence: a myth or coming reality? elba.romero 2018-10-19 01:17
- Virtual Bioequivalence: an update from PAGE (+TSD!) mittyri 2019-06-21 13:50
- FDA not concerned about the type I error? Helmut 2019-06-22 18:11
- Virtual Bioequivalence: a myth or coming reality? Helmut 2021-12-23 22:31
- Synovia is a nasty beastmittyri 2021-12-24 13:23
- Synovia is a nasty beast dshah 2022-01-10 15:31
- Synovia is a nasty beastmittyri 2021-12-24 13:23
- Virtual Bioequivalence: a myth or coming reality? Helmut 2022-02-17 12:06
Ing. Helmut Schütz