Bioequivalence and Bioavailability Forum

Dear ElMaestro!

Thank you very much for your answer and thought-provoking impulse. In my honest opinion, it is not possible to show linear kinetics (it's an assumption) in praxis but we may claim that a product exhibit sufficient dose-proportionality.

I am trying to motivate my questions with the following example:

• Consider a parallel group design where k dose levels (IV route) are investigated
  
• Extremely high variability in the predominant half-life but less variability in AUCs
  
• Dose-proportionality holds evaluated based on AUCs using the power-law model

One question I am trying to answer is: How long does it take that the product is practically (i.e. 99.2% of steady state) eliminated from the body?

To answer this question, an estimate for the predominant half-life is needed as a product is practically eliminated from the body after 7 half-lifes have elapsed.

Is it justified to summarize individual predominant half-lifes over all dose levels to get a single estimate and a confidence interval for the predominant half-life to answer the question above (having in mind that dose-proportionality does not necessarily imply "linear kinetics")?

Best regards

Martin