Peak-to-trough ratio at steady state for a weekly agent

On the subject in the title: Peak-to-trough ratio at steady state for a weekly agent Working notes rather than a conclusion.

Working through the kinetics rather than the pharmacology, because I think the confusion here is arithmetic.

With a half-life of roughly a week, steady state is approached over four to five half-lives, so anything measured before about a month is measuring a rising concentration. Accumulation at weekly dosing lands the steady-state level near double the first-dose level.

Have I got that right, and does it change what people are actually asking?

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.

Bookmarking this. I will come back when I have something worth adding.

Narrowing post #20, because the general version has more than one answer.

A missed weekly dose perturbs a slowly moving average rather than creating a trough. That is the pharmacokinetic reason the labelling does not recommend doubling.

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 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.

This follows post #46 rather than contradicting it.

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.

That much is documented. The rest is how I have interpreted it.

Confirming post #52 from a second method, which matters more than confirming it from a second person.

The practical version of peak-to-trough ratio is three sentences long. The rigorous version is three pages and reaches the same conclusion with the conditions attached.