Bioequivalence and Bioavailability Forum

Dear yvk!

❝ […] specific guidelines available for conducting BE studies on endogenous compounds

No specific guidelines I know of, except from the FDA:
Potassium Chloride, Levothyroxine, Liothyronine, Testosterone, Estrogens.

A baseline-correction must be performed if the compound is known to be present in stable basal levels. Three predose-samples are collected (let's say within 1 hr before administration), and the average is subtracted from the raw-profile. Personally I always recommend to use the median instead of the arithmetic mean.
If the compound is known to be subjected to circadian rhythms, you will have to include another study period, where you measure an entire ‘blank’ profile, which can be used in subtraction.
Any subtraction may lead to negative values in some cases – these values should be set to zero. The corrected profile most likely will show some values below the LLOQ – these values should be taken 'as is'.
Example: LLOQ 0.3, basal 0.4, measured 0.5, corrected 0.1 (not BLQ!).

For some compounds a run-in-period with standardized food (e.g., for potassium chloride) is recommended.

Special attention must also be drawn to potential feedback inhibition of endogenous production.

If the compound has ‘high’ levels compared to ones obtained after administration and is also subjected to variation due to the menstrual cycle (e.g., estriol), a study in postmenopausal women is recommended.

You should pay attention on sequence effects; have a look at FDA's guideline, Section VII.B.