Bioequivalence and Bioavailability Forum

Hi John,

❝ how come observed AUClast and AUCall only have 6 significant figures (unless the last digit is 0) while predicted AUClast/AUCinf, observed AUCinf have full 12 significant figures?

It all depends on the number of significant figures you have for concentrations, the blood sampling times, the method used to calculate AUC, and how Phoenix displays zeros. I assume you're using the linear trapezoidal method (which will make Helmut scream, but that's another topic, just like why you want to have 12 significant figures).

Let's imagine that you have 4 significant figures for concentrations. If you have sampling times at exact hours: each AUC "slice" will have 4 or 5 significant digits (average of the two concentrations x time between the two points). If you have half-hours or quarter hours: possibly 1 or 2 extra figures. If you have a sampling time which does not result in a round decimal value (e.g. 20 minutes = 0.33333[...]33 hours): then you can get 12 significant figures.

For instance, it the concentration at 1h is 1234 and the concentration at 2h is 2345: that "slice" of AUC will be ((1234 + 2345)/2) x (2-1) = 1789.5. That's 5 significant figures. If you want more, all you'll get is extra zeros (1789.50000000). These zeros are significant figures, granted. But I don't know whether they will be displayed in Phoenix.

Predicted values and AUCinf rely on the calculated elimination rate constant, and you can get 12 decimal figures.