Bioequivalence and Bioavailability Forum

Hi everybody

We have just finished the 4th study of Levothyroxine from the same manufacturer, on the strenghts of 25 ug, 63 ug, 100 ug and 200 ug. Only the 25ug presented a sequence effect. Someone here raised a question about the amount of tablets administered in that study, and if it may have any impact that could have caused the sequence effect. In order to use a dosage of 600 ug, 24 tablets had to be administered to the subjects. Is it possible that the high amount of tablets have caused a different response? Maybe some of the tablets did not release the drug immediatelly, causing a retard effect that affected the second period data, or something like that. Besides that, someone mentioned to me a "Memory effect", in which the human body learns how to deal with the drug, causing a different reaction at the second administration. I personally think that this is very hard to happen at only 1 single dose administration.