Yes, there is an effect of enzyme inhibition kinetics, However, drug like curcumin have shown the variable effects with same dose and formulation. It is reported that curcumin case is too different than other drugs.

When you have non-linear PK, the best is to use M&S. The simple dose normalisation is may be not appropriate since comples dose-relationship exists.

Thank you all for your input

Hi.

I don't know the particulars of your application, but one general comment may be of interest.

For nonlinear PK, the dose and AUC are not expected to show dose proportionality, but there is a little more than that. The source of the dose proportionality can influence what you see. For instance, nonlinear clearance vs. nonlinear absorption (using an oral dosage form just as an example) may display different nonlinear behaviors. A similar consideration may apply to dosage forms with different release mechanism, extents and rates.

I guess the bottom line is that is might be worth looking at the normalized Cmax or AUC... just because they normalized values are not close to constant does not mean there is nothing to see, especially when comparing different dosage forms.

Hope this is of interest!

Paul Tanswell

It gets tricky when it comes to liposomal curcumin, curcumin micelles, micronised and phytosome curcumin, of which there aren't many studies testing the same formulation at different doses and these are the formulations I mainly want to compare.

The ultimate goal is to measure one particular liposomal curcumin against all available enhanced formulas (micellised, micronised and phytosomes).

"If you find dose proportionality over the entire dose range and range of literature studies you are looking at, then normalizing by the dose will allow you to compare the formulations." - So for me to compare formulations of curcumin accurately, I need to pick one formulation, gather articles on this formulation which use different doses, plot the mean AUC and Cmax from each study at the different doses on one graph and determine dose proportionality?

I understand your answer but I have some questions;

Do I need to include AUC or can I just use Cmax?

What is the minimum amount of data points I need for different doses?

What if there are only 2 studies that use different doses?

(I'm assuming it is not possible to do if only one study exists on a formulation)

Once plotted a range of doses on a graph for say Cmax of micellised curcumin, do I need a statistical analysis such as linear regression to finalise to determine proportionality?

Thank you for your input it is valued greatly.