Bioequivalence and Bioavailability Forum

Hi Mauricio,

❝ Is possible a study to Brinzolamide with pharmacokinetic endpoint or the fact that Brinzolamide is a carbonic anhydrase inhibitor decreases aqueous humor secretion is the reason to this impossibility ?

You're right PK may be a viable possibility. It is true that B. will decrease the aqueous humour and thus the measured concentration is in a sense a complex PD-endpoint as well as a PK-endpoint. But hey, if two products are bioequivalent thenthe phenomenon should affect both formulations equally and you'll be OK.
But i think the real reason for the difference in endpoint choice for Prednisolone and Brinzolamide is associated to a well-founded regulatory concern for the trial subjects; it isn't great fun for a trial subject when someone pokes a needle into her/his eye to drain some fluid every now and then. After period 1 when the PI says "Thank you, Mr Jones, for allowing us to mutilate your right eye today. Next week we'll have great fun with the left eye.", Mr Jones might be slightly inclined to withdraw his consent and run for the hills (actually he might not even do it in that order).
So when a noninvasive endpoint method is available, like intraocular pressure for Brinzolamide then by all means that's what you want to do. For Prednisolone there is no PD-endpoint, at least no well-defined and validated one, to the best of my knowledge. If there were I am quite certain FDA's guidance would change.