Time to steady state after a dose increase

On the subject in the title: Time to steady state after a dose increase 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?

The arithmetic in post #11 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.

Someone will know this better than I do and I hope they say so.

Coming back to post #15, because the follow-up matters more than the original answer.

Loading doses are not used in this class and the pharmacokinetic reason is tolerability rather than efficacy. A loading dose would reach steady state faster and would be intolerable.

Post #22 and I disagree about the size of the effect, not about the direction.

Fasting requirement for oral semaglutide: food and large fluid volumes reduce absorption. The fasting window (30 minutes before and 30 minutes after) is designed to maximise absorption. Violating it measurably reduces exposure.

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

Where I part company with post #55, and it is a narrow parting.

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

Not a strong opinion, just a consistent one.

Fasting requirement for oral semaglutide: food and large fluid volumes reduce absorption. The fasting window (30 minutes before and 30 minutes after) is designed to maximise absorption. Violating it measurably reduces exposure.

Post #116 and I disagree about the size of the effect, not about the direction.

Between-person variability in exposure is substantial and is the reason two people on the same dose can have quite different plasma concentrations. That is inherent rather than a formulation defect.

That is what the documentation says. What happens in practice is usually close.

I had written a reply contradicting post #134 and deleted it. Here is what survived.

The time to maximum concentration after a subcutaneous dose in this class is measured in days rather than hours, which surprises people expecting an injection to act quickly.

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.

For what it is worth, the same held on the two occasions I checked.