Bioequivalence and Bioavailability Forum

Hi Mittyri,

sorry for excavating such an old post.

» AFAIK regulatories are also interested and funding some of them.

See here and the back-story by authors of the FDA.*

» What do you think?

In my CRO I had the displeasure to deal with topical diclofenac. Low plasma concentrations doable by GC/MS with stable isotope IS but extremely variable. Really ugly profiles. Synovia was as close to a nightmare you can get. How to sample without contamination? We tried a lot of crazy stuff (cleaning the skin with acetone and isopropanol, skin stripping, …). Nothing worked. We ended up in patients scheduled for a total knee arthroplasty. Recruitment not easy “Why should I apply the cream daily under occlusion for three weeks when my knee is cut off anyway?” Turned out that >50% had a so-called ‘dry knee’, i.e., no synovia at all. Bad luck.
Given all that, I’m asking myself on which data the FDA’s model is based upon and how reliable they are. 

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• Tsakalozou E, Babiskin A, Liang Zhao L. Physiologically-based pharmacokinetic modeling to support bioequivalence and approval of generic products: A case for diclofenac sodium topical gel, 1%. CPT Pharmacometrics Syst Pharmacol. 2021; 10(5): 399-411. doi:10.1002/psp4.12600. Open access.