Bioequivalence and Bioavailability Forum

Dear Nobody

❝ eehm I didn'T read the original article (only abstract), but half of the relevant parameters are not identifiable without i.v. data... sorry, but have seen so much nonsense PK evaluations even in the assessment reports published by FDA etc. over the years, don't buy this EHR without additional data.

Ok. One stupid question
"How to determine the absolute bioavailability of drugs as ezetimibe which are virtually insoluble in aqueous media suitable for injection?"

IMHO, in those cases you have to rely on the oral IR tablet/suspension data.

Where extensive glucuronidation in the lumen and liver is involved (leading to formation of glucuronide metabolite), there will be high chances or occurence of hepatic recirculation.

Also, the movement of bile acids in the EHC fluctuates, accelerating with meals and decelerating during fasting. The movement of the EHC is largely determined by the activity of its mechanical pump, the small intestine, whose motility is governed by neurohormonal factors initiated by entrance of food into the small intestine from the stomach. Thus for all practical purposes the “rhythm” of the EHC is determined by the duration of gastric emptying, which in turn is determined by the eating pattern and dietary content. Contraction of the gallbladder is essential for mobilizing the stored bile acids but is not critical for further movement of bile acids, which depends on intestinal propulsion.

Thus if the multiple peak is occurring around the meal time (stimuli for bile secretion, one can see it around 4-6 hr post dose during lunch time, 8 -10 hrs post dose around snacks time and 12-14 hrs post dose around dinner time), it most probably will be because of EHC as food acts as stimuli for bile acid secretion.



Would be happy if someone can correct me if I got this one wrong.