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ForumsDosing & ProtocolsPK/PD modeling for tirzepatide — looking for input Page 2

PK/PD modeling for tirzepatide — looking for input

Dr.EndoIndy Tue, Jun 25, 2024 at 7:43 PM 15 replies 1,918 viewsPage 2 of 3
stefan_berlin
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Jun 25, 2024 at 11:23 PM#6

One concrete data point for the thread. Numbers worth memorising for this class: Tmax one to three days for the weekly peptides, terminal half-life about a week for semaglutide and about five days for tirzepatide, steady state at four to five half-lives, subcutaneous bioavailability high enough that site choice is irrelevant.

Worth separating that from the pharmacology, which this thread keeps folding into the same question. They behave differently and the advice does not transfer.

36 6NeuroNate, JessicaH_TX, KevinCompounds and 33 others
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PedsEndoPhilly
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Jun 26, 2024 at 12:49 AM#7

Following on from sophie_paris — and this may be the naive question:

Whether anyone has held 10mg long term rather than climbing, and what happened over the following year?

Last edited: Jun 26, 2024 at 5:49 AM
35 5wendy_avl, jason_paloalto, Dr.LeslieOBGYN and 32 others
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pat_auckland
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Jun 26, 2024 at 2:15 AM#8
stefan_berlin said:
Numbers worth memorising for this class: Tmax one to three days for the weekly peptides, terminal half-life about a week for semaglutide and about…

Coming at stefan_berlin’s question from a different direction. The pharmacokinetics explain nearly every practical question asked here. Albumin binding above 99% slows clearance enough to make weekly dosing possible; a terminal half-life near a week means four to five weeks to steady state and therefore a four-week titration interval; subcutaneous bioavailability around 89% means injection site barely matters. Those three facts answer most timing questions before they are asked.

34 4LarryQC_SD, wanda_boise, NurseAsh_DET and 31 others
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Dr.EndoIndy
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Jun 26, 2024 at 3:41 AM#9

OP back with an update, since a thread like this is useless without one.

Update: the eight-week restart pattern people described is exactly what happened. I nearly abandoned it at week five.

33 3DeniseRN_TPA, SandraNC_45, Dr.EndoIndy and 30 others
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JessicaH_TX
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Jun 26, 2024 at 10:35 AM#10
pat_auckland said:
The pharmacokinetics explain nearly every practical question asked here.

True, though the ladder is longer and that is not a neutral detail — six dose steps means six opportunities to stall on the way up, and plenty of people never reach the dose the headline number came from.

Last edited: Jun 26, 2024 at 2:35 PM
31 4tony_orlando, Dr.NephBHM_UK, kim_atl_prep and 28 others
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