Forum Replies Created
April 28th Webinar: Considerations for Management of Clinical Trials and Regulatory Filing Strategy in Light of COVID-19
Good to hear from you again.
While one could use a “kinetics of drug effects” approach, I have not seen it used for herbal drugs. What would be the research question that you’d want the model to answer?
See this description by Jacqmin et al https://www.ncbi.nlm.nih.gov/pubmed/17051439
Here a virtual compartment representing the biophase in which the concentration is in equilibrium with the observed effect is used to extract the (pharmaco)kinetic component from the pharmacodynamic data alone. Parameters of this model are the elimination rate constant from the virtual compartment (KDE), which describes the equilibrium between the rate of dose administration and the observed effect, and the second parameter, named EDK50 which is the apparent in vivo potency of the drug at steady state, analogous to the product of EC50, the pharmacodynamic potency, and clearance, the PK “potency” at steady state.
My co-authors and I used this approach for a bisphosphonate – see DOI: 10.1111/j.1365-2125.2004.02224.x
You could also check out the work described in Gabrielson and Weiner’s textbook on Dose-Response-Time models, and applications in a few cases including ophthalmology.
Let us know how this works out,
Yes – this will be better. Chloroquine concentrates in red blood cells and would be a relevant example based on the discussions in the webinar.
In this situation, serum or plasma concentrations are less than the red blood cell concentrations, with haematocrit (Hct) as the adjustment factor. I saw average partitioning as being in a ratio is 1 : 3
However, given that there is between individual variability in Hct – it makes sense to measure the whole blood concentration directly if your lab has the assay.