Volume of distribution: the theoretical volume the drug distributes into. For albumin-binding compounds, volume is reduced compared to drugs that do not bind protein. That is relevant to understanding how much free drug is available.
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Pharmacology · Pharmacokinetics · continued
Half-life, steady state, and accumulation worked through — a second dataset posts 61–90
This is a continuation of a long topic, addressed by post number rather than by page. Start at post 1.
Picking up post #59: that is the part I would want checked first.
Hepatic metabolism: the degree to which each compound is hepatically metabolised versus renally cleared is known but varies. Severe liver disease changes clearance.
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y.adeyemi, post #48: Thank you for the correction. I have edited my earlier post with a note rather than silently, so the thread still makes sense to read. The error was mine and it was the kind that comes from remembering a figure instead of looking it up. Go to post
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.
taper_table, post #34: Coming back to post #32, because the follow-up matters more than the original answer. Bioavailability: oral semaglutide has low bioavailability (roughly 1%) due to peptide instability. That is why the oral dose (14 mg) is so much larger than the injectable dose. Comparing them by mass is meaningless. Go to post
For anyone arriving from a search: the marked solution above is the direct answer, and the replies underneath it add the caveats that make it safe to use.
I read post #63 twice before replying, because I had assumed the opposite.
Two things before anyone answers the substance.
First, the context in the first post is clear and specific. Second, the question is framed so that an answer can actually address it. Both are the norm here and both matter more than they sound.
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This follows post #63 rather than contradicting it.
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.
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SNAC (the oral bioavailability enhancer): sodium N-(8-[2-hydroxybenzoyl]amino) caprylate transiently raises gastric pH and promotes absorption. Without it, oral bioavailability is too low for clinical use. With it, bioavailability is still variable between people.
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s.kuusela, post #44: Picking up post #41: that is the part I would want checked first. Individual variation: people vary in how quickly they absorb, distribute, metabolise, and excrete these compounds. That variation is partly genetic and partly due to individual biology (gut motility, kidney and liver function). It explains why two people on the same dose… Go to post
Bioavailability: oral semaglutide has low bioavailability (roughly 1%) due to peptide instability. That is why the oral dose (14 mg) is so much larger than the injectable dose. Comparing them by mass is meaningless.
Coming back to post #67, because the follow-up matters more than the original answer.
Albumin binding: semaglutide binds albumin through a fatty side chain, which sequesters the free form and extends the half-life. Tirzepatide also has albumin binding (different mechanism) which extends its half-life compared to an unmodified peptide.
17 likes 6mo
m.balogun, post #14: Worth separating two things that post #10 runs together. Volume of distribution: the theoretical volume the drug distributes into. For albumin-binding compounds, volume is reduced compared to drugs that do not bind protein. That is relevant to understanding how much free drug is available. Go to post
Thank you for the correction. I have edited my earlier post with a note rather than silently, so the thread still makes sense to read. The error was mine and it was the kind that comes from remembering a figure instead of looking it up.
post #70 is right about the mechanism and I think understates the practical bit.
Individual variation: people vary in how quickly they absorb, distribute, metabolise, and excrete these compounds. That variation is partly genetic and partly due to individual biology (gut motility, kidney and liver function). It explains why two people on the same dose have different response magnitudes.
0 likes 6mo
ai.vukovic, post #18: On post #14 — agreed on the reasoning, with one qualification. Albumin binding: semaglutide binds albumin through a fatty side chain, which sequesters the free form and extends the half-life. Tirzepatide also has albumin binding (different mechanism) which extends its half-life compared to an unmodified peptide. Go to post
Worth separating two things that post #68 runs together.
Having read the exchange above, I think I was wrong earlier in this topic and I want to say so plainly rather than quietly editing.
The correction was fair and I had been repeating something I had not checked carefully enough.
taper_table, post #34: Coming back to post #32, because the follow-up matters more than the original answer. Bioavailability: oral semaglutide has low bioavailability (roughly 1%) due to peptide instability. That is why the oral dose (14 mg) is so much larger than the injectable dose. Comparing them by mass is meaningless. Go to post
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.
Renal clearance: these compounds are cleared partly via the kidney. In severe renal impairment, clearance is slowed and accumulation risk is higher. Dose adjustments might be needed.
24 likes 6mo
post #74 answers the question as asked. The question underneath it is different.
Bioavailability: oral semaglutide has low bioavailability (roughly 1%) due to peptide instability. That is why the oral dose (14 mg) is so much larger than the injectable dose. Comparing them by mass is meaningless.
0 likes 6mo
l.osei, post #26: Hepatic metabolism: the degree to which each compound is hepatically metabolised versus renally cleared is known but varies. Severe liver disease changes clearance. Go to post
SNAC (the oral bioavailability enhancer): sodium N-(8-[2-hydroxybenzoyl]amino) caprylate transiently raises gastric pH and promotes absorption. Without it, oral bioavailability is too low for clinical use. With it, bioavailability is still variable between people.
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.
7 likes 6mo
Coming back to post #76, because the follow-up matters more than the original answer.
Albumin binding: semaglutide binds albumin through a fatty side chain, which sequesters the free form and extends the half-life. Tirzepatide also has albumin binding (different mechanism) which extends its half-life compared to an unmodified peptide.
17 likes 6mo
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.
25 likes 6mo
Renal clearance: these compounds are cleared partly via the kidney. In severe renal impairment, clearance is slowed and accumulation risk is higher. Dose adjustments might be needed.
0 likes 6mo
Worth separating two things that post #77 runs together.
Hepatic metabolism: the degree to which each compound is hepatically metabolised versus renally cleared is known but varies. Severe liver disease changes clearance.
18 likes 5mo
Volume of distribution: the theoretical volume the drug distributes into. For albumin-binding compounds, volume is reduced compared to drugs that do not bind protein. That is relevant to understanding how much free drug is available.
7 likes 5mo
s.karlsen_rph, post #69: Coming back to post #67, because the follow-up matters more than the original answer. Albumin binding: semaglutide binds albumin through a fatty side chain, which sequesters the free form and extends the half-life. Tirzepatide also has albumin binding (different mechanism) which extends its half-life compared to an unmodified peptide. Go to post
Individual variation: people vary in how quickly they absorb, distribute, metabolise, and excrete these compounds. That variation is partly genetic and partly due to individual biology (gut motility, kidney and liver function). It explains why two people on the same dose have different response magnitudes.
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.
25 likes 5mo
Individual variation: people vary in how quickly they absorb, distribute, metabolise, and excrete these compounds. That variation is partly genetic and partly due to individual biology (gut motility, kidney and liver function). It explains why two people on the same dose have different response magnitudes.
12 likes 5mo
trough_index, post #81: Worth separating two things that post #77 runs together. Hepatic metabolism: the degree to which each compound is hepatically metabolised versus renally cleared is known but varies. Severe liver disease changes clearance. Go to post
Volume of distribution: the theoretical volume the drug distributes into. For albumin-binding compounds, volume is reduced compared to drugs that do not bind protein. That is relevant to understanding how much free drug is available.
Collapsed as off-topic by two members at trust level 3 or above
Picking up post #85: that is the part I would want checked first.
Hepatic metabolism: the degree to which each compound is hepatically metabolised versus renally cleared is known but varies. Severe liver disease changes clearance.
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.
0 likes 5mo
For anyone arriving from a search: the marked solution above is the direct answer, and the replies underneath it add the caveats that make it safe to use.
17 likes 5mo