Bioequivalence and Bioavailability Forum

Hi Babe_Ruth,

❝ ❝ Bad practice to force BQLs after tmax to zero

❝

❝ What about for sparse sampling methods?

Sparse sampling is another cup of tea. Sounds trivial but actually isn’t.

❝ If there are 3 samples/time point, wouldn't we want to use 3 values for the calculation of the mean concentration? In which case imputing BQL concentrations with a value of 0 or close to 0 would be more favorable than not including the value altogether?

Some ideas:

• Phoenix/WinNonlin supports only the linear trapezoidal rule for spare sampling. Hence, anything is possible.
  
• Imputing 0 for post dose BQLs goes against the grain for me. Most commonly used is LLOQ/2. But why the heck divide by two? What I would do: Try to get an idea of the PK (well, difficult in the first TK-study of a drug). Perform simulations and based on the LLOQ & sampling schedule come up with a reasonable ratio.
  
• Try also the R-package PK* which contains more methods for sparse sampling designs than PHX/WNL.
  Both authors are members of the forum. I’ll notify them; maybe they can jump into the discussion.

❝ […] I'm interested in learning more about what I'm doing.

  Basic research is what I’m doing
when I don’t know what I’m doing.   Wernher von Braun

❝ Browsing these forums in my spare time really helps me see where others are in environment of the Ba/Be world :) Searching old topics have answered most of the questions I have had, which is super helpful.

Maybe you can convince your employer to browse the forum in your payed time…

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• Jaki T, Wolfsegger MJ. Estimation of pharmacokinetic parameters with the R package PK. Pharm Stat. 2011;10(3):284–8. doi:10.1002/pst.449.