Bioequivalence and Bioavailability Forum

Dear Taresh,
There are many people with more experience of your problem on this board however as it's been quiet I will make a couple of suggestions. The best way to assess the impact of sampling time point selection is to Simulate the trial with different schedules. If you overlay the time-conc plots you will see how Cmax, Tmax & AUC can be affected very easily. I would also review the partial derivative plots for each parameter.

Furthermore you can use diagnostic parameters e.g. VIF (Variance Inflation Factor - available in WinNonlin etc.) to assess 'objectively' the better schedule to best estimate your parameters of interest since there will always be a compromise.

I can suggest a free webinar that discuss some of the problems so might be useful to you as background;
"Critical Path Approach for Development of Generic Products"

During this presentation some suggestions are made that maybe useful for you to bear in mind;

Absorption phase should include 3-5 sampling time points
Cmax region should include 4-8 sampling time points (remember Cmax/Tmax is often the most variable and easy to 'miss')
Distribution and Elimination phases should include 4-10 sampling time points

If you take the maximum of all of these you have 23 timepoints; generally I would expect some trade-off but overall I would aim that the length of sampling schedule should be at least 4-5 half-life of drug to accurately assess total AUC (so AUClast is >80% AUCinf).

Simon.