Posting this under the heading it deserves: Washout: how long is long enough, and for what purpose Everything below is what sits behind that.
A narrow question about Washout, deliberately narrow, because the broad version has been asked here four times and produced four long threads and no answer.
One question, stated units, stated method, and what I have already ruled out.
Where I part company with the opening post, and it is a narrow parting.
An observation about Washout that I cannot explain and am posting anyway, on the principle that unexplained observations are more useful public than private.
Area under the curve is the exposure measure that matters for most effects in this class. Peak concentration matters more for tolerability.
Metabolism for peptide drugs is proteolytic rather than hepatic in the usual sense, which is why the cytochrome interaction questions that dominate small-molecule pharmacology mostly do not apply.
That much is documented. The rest is how I have interpreted it.
Building on post #4 rather than restating it.
The documentation on Washout is better than this thread and I say that as someone who has posted in the thread.
Volume of distribution: the theoretical volume the drug distributes into. For albumin-binding compounds, volume is reduced compared to drugs that do not bind protein. That is relevant to understanding how much free drug is available.
I would rather say I do not know than round it up to an answer.
Helpful, and easy to find again, which is half of what a good reply is.
What I would check first on Washout is whether the thing being measured moved or whether the way of measuring it moved. Those look identical in a graph.
A pharmacokinetic model fitted to trial data describes the population studied. Applying it to somebody outside the enrolled range is an extrapolation, and the model will not tell you it is.
The reasoning is more useful than the number, which is why I have shown it.
On post #9 — agreed on the reasoning, with one qualification.
Washout after stopping takes roughly the same four to five half-lives as reaching steady state. A month after the last dose is not the same as none.
The short answer was in the first line; everything after is the working.
Picking up post #9: that is the part I would want checked first.
The question underneath Washout is usually "how would I tell?" rather than "what is true?", and that one has a method attached to it.
Write down what you would expect to see under each hypothesis before you collect anything. If they predict the same observation, collecting it will not help.
Post #13 describes the usual case. This is about the unusual one.
Where I have landed on Washout, having got it wrong once in public: the direction is clear, the magnitude is not, and anyone quoting a precise magnitude has borrowed it from somewhere that did not measure it.
Small correction to my own earlier position on Washout. I had the units the wrong way round, which changes the conclusion by an order of magnitude and therefore changes it entirely.
Confirming post #17 from a second method, which matters more than confirming it from a second person.
Worth separating Washout as a question about the compound from Washout as a question about the documentation. They get answered by different people and only one of them is answerable here.
Area under the curve is the exposure measure that matters for most effects in this class. Peak concentration matters more for tolerability.
Post #20 put the caveat in the right place and I want to underline it.
What I want from this Washout thread is the list of things that would need to be true for the claim to hold. If we can write that list, we can check it.
On Washout, I would rather understate and be corrected upward than overstate and be quoted. That is a house style here and it is a good one.
Post #26 is right about the mechanism and I think understates the practical bit.
Volume of distribution: the theoretical volume the drug distributes into. For albumin-binding compounds, volume is reduced compared to drugs that do not bind protein. That is relevant to understanding how much free drug is available.
Coming back to post #28, because the follow-up matters more than the original answer.
Washout was covered in the wiki last year and the page has a review date on it, which is a better starting point than my memory of a thread.