Bioequivalence and Bioavailability Forum

Dear all!

Motivated by a recent discussion with HS I would like start a thread regarding "rather" basic principles of pharmacokinetics:

1. On assumptions of linear kinetics, PK parameters such as half-life(s) and clearance are per definition constant for different dose levels and observed differences are simple due to variability only (correct?)
   
2. Linear kinetics implies dose-proportionality but not necessarily vice versa (correct?)
   
3. In practice, we are not able to "show" linear kinetics but we can assess dose-proportionality (correct?)

In the case that dose-proportionality was shown over a dose-range, is it then justified to summarize for example individual half-life(s) over all dose ranges investigated to get a "better" estimate (i.e. based on a larger sample size leading to narrower confidence intervals) ?

Best regards

Martin