Half-life, steady state, and accumulation worked through

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.

Filing this under things that are true until someone shows me otherwise.

Half-life determines how quickly concentration approaches steady state and does not determine what the steady-state concentration is. Dose and clearance determine that.

That is the shape of it. The detail is where I would expect to be corrected.

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.

That is clearer than the version I had in my head. Thank you.

Accumulation at steady state: with a week-long half-life, steady-state concentration is reached around 4 to 5 half-lives (about 4 to 5 weeks). Before that, concentration is rising with each dose. The clinical implication: escalating before 4 weeks means escalating before steady state.

I have seen it go both ways, which is why I hedge.

No disagreement from me. Posting only so the question does not look ignored.

Taking post #79 at face value and following it one step further.

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.

Take it as a starting point and not as a specification.

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.

I checked the source rather than the summary, and they differ.

This settles it for me, at least until somebody posts a reason it should not.