Adding what did not work for me on albumin binding, since the failures never get written up and they are half the useful information.
26 likes 18mo
Topic summary
Albumin binding and how it produces a long half-life
This is a generated summary. It shows the 6 most-liked posts from a topic of 45, in their original order, with the accepted answer included where one exists. It is a reading aid and it will miss nuance — the full topic is the record.
a.villalobos, post #7: Answering the question post #4 raises rather than the one it answers. 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. Go to post
The arithmetic in post #19 is right; the assumption feeding it is the part to check.
The accumulation ratio for weekly dosing with a week-long half-life is around two, which is why the concentration after several doses is roughly double the concentration after the first.
I disagree with the framing of albumin binding 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.
24 likes 15mo
baseline_table, post #4: Adding the measurement that post #2 says would settle it. 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. Go to post
Albumin binding: semaglutide binds albumin through a fatty side chain, which sequesters the free form and extends the half-life. Tirzepatide also has albumin binding (different mechanism) which extends its half-life compared to an unmodified peptide.
Worth one more sentence than it usually gets.
That is the distinction I keep failing to hold on to. Written down now.
33 likes 14mo
Terminal half-life estimated from a short sampling window underestimates the true value. That is a common source of discrepant figures between sources.
27 likes 14mo
Read the full topic (45 posts)
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