Bioequivalence and Bioavailability Forum

Dear HS
Thank you for your kind comments.

I would like to add something here.
As i understand washout periods are meant to "wash out" the drug from the body, completely remove it, or as nearly completely as possible (correct me here if I am wrong). Most PK scientists would tell us that the consensus on five half lives for washout period came from the fact that 96.9 % of the drug has been removed from the body by the time five half lives are over. Of course some regulatory bodies give you the option of applying at least three half-lives that emcompasses both washout and run-up. By three half-lives, 87.5% of the drug is lost, by four half-lives 93.5% of the drug is removed. So i guess if you are happy with 87.5 %(=three half-lives) of the drug lost from the body, no problems in accommodating with the design they suggest. Whether you call it "washout period" or "build-up", they are meant to remove the drug from the body. I meant it in that simple sense. I think the operative word here is "at least"; the regulatory recommends a lower margin, and puts no tabs on the upper margin. Its upto the sponsor to arrive on a judicious upper margin, balancing the effects of subject dropout and unacceptable results.
I did not know about the "switchover design" you are talking about. thanks for telling me. I will check it out.
When you say

❝ Forget about washouts in steady-state; they are just a waste of time, increasing the chance of subjects dropping out from the study

do you mean you are totally against washout periods in biostudies involving steady state???? I wonder how this statement would go down with Ethics Committees??? And you have to agree that the regulatory bodies, in general, recommend a longer washout in steady-state studies as compared to single dose studies.

❝ you would get the same plasma concentrations no matter what initial concentration you start with.

I am afraid i don't think this can be treated as a blanket statement, though it may be true in most cases. How will you explain drug toxicity then??? what about specifically those drugs that accumulate on steady state dosing? I believe that is a major function of "therapeutic drug monitoring".
OK, about DKMA I think i misunderstood the date as 2007 instead of 2006. But my focus was not on the date but on the contents of the directive. I was merely commenting on how people would like to interpret guidelines in a crooked manner.

Regards

Shabana N.

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Edit: Full quote removed. [HS]