Topic summary

Splitting a weekly dose in two: the pharmacokinetic argument against — the long version

Practice › Dosing & titration dose reduction semaglutide titration Wiki

This is a generated summary. It shows the 9 most-liked posts from a topic of 149, 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.

s.lundgrenTL28 Jul 2024#45

g.haaland, post #16: Holding a dose indefinitely: the trials did not study indefinite holding at a non-maximum dose. The trials escalated to a target and then held that. What happens if you stay at an intermediate dose for years is not formally studied and extrapolation is the best available reasoning. Go to post

Post #44 answers the question as asked. The question underneath it is different.

Speaking only to Splitting a weekly dose 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.

30 likes in reply to #16 2.1y

cannula_driftTL3Regular8 Jul 2024#68

Concentration and dose get conflated constantly in this subcategory. Changing how much diluent you add changes the volume you draw and changes nothing about the dose.

That is a description of practice, not a recommendation of it.

32 likes 2.1y

KTurkingtonTL3Regular8 Jul 2024#71

h.eriksen, post #27: Dose and effect are not linear across the studied range for every compound in this class. Assuming a doubled dose gives a doubled effect is the reasoning error behind most disappointment. Adding it in case it saves somebody the afternoon it cost me. Go to post

Everything in post #67 holds. The case it does not cover is the one I have.

The version of Splitting a weekly dose that circulates here is a simplification of a simplification. It is not wrong, but it has lost the conditions under which it holds, and those conditions are where the interesting cases live.

31 likes in reply to #27 2.1y

a.reyesTL4 Admin9 Jul 2024#80

journalclub_wren, post #29: Picking up post #26: that is the part I would want checked first. Steady state means the plasma concentration is stable from dose to dose. That happens around 4 to 5 half-lives. Before that, the concentration is rising with each dose. Escalating before steady state means escalating on incomplete information about the dose you are on.… Go to post

Post #79 is right about the mechanism and I think understates the practical bit.

A missed dose in a weekly schedule is not a trough to chase. With a week-long half-life you are perturbing a slowly moving average, and the labelling for licensed products in this class says take it if the next dose is far enough away and skip it otherwise.

Flagging that the sources on this are thinner than the confidence in the thread suggests.

30 likes in reply to #29 2.1y

r.venkatesanTL3Wiki editor9 Jul 2024#88

Escalating before steady state means you are judging a dose you have not yet fully experienced. That is the whole argument against compressing the schedule and it is a good one.

I am reporting what happened, not recommending it.

32 likes 2.1y

BBramleyTL3Regular9 Jul 2024#96

The arithmetic in post #94 is right; the assumption feeding it is the part to check.

Going back down a step is not a failure and the trials allowed it. Several protocols permitted a return to the previous dose for tolerability and then a second attempt at the step.

A guess, clearly labelled as one.

30 likes 2.1y

r.lundgrenTL210 Jul 2024#112

h.fonseca, post #41: I will take the caveat as seriously as the claim, which is the point of putting it there. Go to post

Splitting a weekly dose is one of those subjects where the general answer and the answer for a specific case diverge, and the thread will go in circles until someone says which one is being asked for.

29 likes in reply to #41 2y

k.redgraveTL2Member10 Jul 2024#119

Titrating on tolerability rather than on the calendar: some people escalate when they tolerate a dose well, others escalate on the prescribed schedule regardless. The published trials used a calendar-based schedule. Tolerability-based escalation has no formal evidence base but is not uncommon in practice.

28 likes 2y

d.eriksenTL210 Jul 2024#123

r.venkatesan, post #88: Escalating before steady state means you are judging a dose you have not yet fully experienced. That is the whole argument against compressing the schedule and it is a good one. I am reporting what happened, not recommending it. Go to post

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

31 likes in reply to #88 2y

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