Pharmacology · Pharmacokinetics · continued

Coming back to: Washout: how long is long enough, and for what purpose posts 31–60

Pharmacology › Pharmacokinetics missed dose semaglutide worked example Closed

This is a continuation of a long topic, addressed by post number rather than by page. Start at post 1.

l.oseiTL22 Feb 2026#31

b.vestergaard, post #12: 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… Go to post

I changed my mind about Washout after someone here asked me for the source and I could not produce one. That is worth saying out loud because it is the ordinary way it happens.

31 likes in reply to #12 6mo

m.restrepoTL23 Feb 2026#32

Collapsed as off-topic by two members at trust level 3 or above

The arithmetic in post #31 is right; the assumption feeding it is the part to check.

Area under the curve is the exposure measure that matters for most effects in this class. Peak concentration matters more for tolerability.

I looked this up rather than remembered it, which is the right order.

d.bakkerTL24 Feb 2026#33

Post #31 put the caveat in the right place and I want to underline it.

On Washout, the part that usually goes wrong is that the question is asked as though it has one answer. It has a range, and the width of the range is the interesting bit.

If you can post the two or three numbers you are working from, several people here will check the arithmetic rather than argue about the conclusion.

3 likes 6mo

a.asanteTL25 Feb 2026#34

Adding thanks rather than a view. I do not have a view worth the space.

0 likes 6mo

OstrowskiTL2Member7 Feb 2026#35

a.cardoso, post #10: 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. Go to post

The most useful thing anyone has posted about Washout in this category was a table of what had been measured and by whom. That is what I would want again.

23 likes in reply to #10 6mo

h.nwosuTL28 Feb 2026#36

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.

It is the sort of thing that seems obvious in retrospect and was not at the time.

10 likes 6mo

ThibodeauTL3Regular9 Feb 2026#37

Post #35 and I disagree about the size of the effect, not about the direction.

A note on scope: what I am saying about Washout applies to the case in the first post and I would not extend it further without checking.

1 like 6mo

j.silvaTL210 Feb 2026#38

Taking post #35 at face value and following it one step further.

Where the Washout reasoning breaks down for me is the step from the group result to the individual case. That step is almost never argued for.

0 likes 6mo

c.boatengTL211 Feb 2026#39

I read post #35 twice before replying, because I had assumed the opposite.

Where two sources give different half-lives, check the study design before deciding either is wrong. Sampling duration, assay sensitivity and population all move the number.

16 likes 5mo

mira.patelTL4 Admin12 Feb 2026#40

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.

6 likes 5mo

r.weissTL213 Feb 2026#41

SHermansen, post #5: 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. Go to post

The arithmetic in post #40 is right; the assumption feeding it is the part to check.

Practical answer on Washout, since the theoretical one is upthread: do the simplest check first, write down the result, and only then decide whether the complicated explanation is needed. It usually is not.

23 likes in reply to #5 5mo

aliquot_lineTL3Regular14 Feb 2026#42

Answering the question post #38 raises rather than the one it answers.

Genuine question rather than a rhetorical one: has anyone here actually observed Washout, as opposed to read about it? The thread is long and I cannot tell.

0 likes 5mo

v.stanescuTL215 Feb 2026#43

Half-life: semaglutide ≈ 165–184 hours (about a week). Tirzepatide ≈ 5 days. Liraglutide ≈ 13 hours. The half-life determines how much accumulation happens at steady state and how long it takes to clear after stopping.

1 like 5mo

NicolaidesTL3Regular16 Feb 2026#44

a.asante, post #34: Adding thanks rather than a view. I do not have a view worth the space. Go to post

Second this, and I would have said it less carefully.

6 likes in reply to #34 5mo

f.piresTL217 Feb 2026#45

a.westergaard, post #1: 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… Go to post

A methods point on Washout rather than a substantive one: if the comparison is not like for like, the difference you are measuring is the difference in method.

17 likes in reply to #1 5mo

glossary_deskTL3Regular18 Feb 2026#46

Everything in post #42 holds. The case it does not cover is the one I have.

Two people in this thread mean different things by Washout and are disagreeing about the definition while believing they are disagreeing about the facts. Worth pausing to define it.

32 likes 5mo

d.achebeTL219 Feb 2026 · edited#47

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.

I have changed my mind on this once already, so take it as current rather than settled.

0 likes 5mo

DKwiatkowskiTL3Regular20 Feb 2026#48

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.

3 likes 5mo

j.lokkenTL221 Feb 2026#49

Nicolaides, post #44: Second this, and I would have said it less carefully. Go to post

Fine by me. I had wanted a stronger conclusion and there is not one available.

0 likes in reply to #44 5mo

taper_fileTL3Regular22 Feb 2026#50

methods_draft, post #7: 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. Go to post

Since Washout keeps coming up, it should probably be a maintained page rather than a recurring thread. I am happy to draft it if someone with more direct experience will review it.

1 like in reply to #7 5mo

glossary_deskTL3Regular23 Feb 2026 · edited#51

m.restrepo, post #32: The arithmetic in post #31 is right; the assumption feeding it is the part to check. Area under the curve is the exposure measure that matters for most effects in this class. Peak concentration matters more for tolerability. I looked this up rather than remembered it, which is the right order. Go to post

On post #50 — agreed on the reasoning, with one qualification.

What would change my mind on Washout is a second dataset collected by someone with no stake in the first. Until then I hold it loosely and I would rather say so than pretend to more.

15 likes in reply to #32 5mo

a.vestergaardTL224 Feb 2026#52

Picking up post #50: that is the part I would want checked first.

Area under the curve is the exposure measure that matters for most effects in this class. Peak concentration matters more for tolerability.

Nothing above should be read as advice about what anyone else should do.

6 likes 5mo

GEldridgeTL3Regular25 Feb 2026#53

Speaking only to Washout as I have actually seen it, rather than as it is usually described: the effect is real, it is smaller than the thread suggests, and the variance between people is larger than the effect.

1 like 5mo

a.krastevTL226 Feb 2026#54

Collapsed as off-topic by two members at trust level 3 or above

Useful. I had the fact and not the reason, which turns out to be the important half.

cohort_notesTL2Member27 Feb 2026#55

taper_table, post #29: 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. Go to post

Source for the Washout figure, since it was asked for. It is in the discussion rather than the abstract, which is why the version circulating is stronger than the paper is.

Reading the surrounding paragraph is worth the two minutes. The authors are more careful than their summarisers.

10 likes in reply to #29 5mo

s.perrinTL228 Feb 2026#56

h.bhattacharya, post #18: 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. Go to post

This follows post #53 rather than contradicting it.

The step people skip is the one I have spelled out.

3 likes in reply to #18 5mo

glossary_checkTL2Member1 Mar 2026 · edited#57

Practical note on Washout: write down what you expect before you look. The number of times I have found what I went looking for is higher than chance would allow.

0 likes 5mo

an.kirchnerTL22 Mar 2026#58

I disagree with the framing of Washout above, and I think it is a substantive disagreement rather than a terminological one. Setting out why, so it can be checked.

The reasoning depends on an assumption that is doing a lot of work and is never stated. If the assumption holds, the conclusion follows. I do not think it holds generally.

30 likes 5mo

t.waldenstrmTL2Member3 Mar 2026#59

Grateful for the specificity. Vague answers to this question are what sent me looking.

29 likes 5mo

f.espinozaTL24 Mar 2026#60

I would put a moderate confidence on that and no more.

15 likes 5mo