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Is 8 mg/mL a sensible working concentration for survodutide, or should I go lower?

Asked 24 Aug 2024Modified 21 months agoViewed 44k times
30

The particulars: 8 mg/mL · survodutide.

I am trying to choose between two options that are usually discussed as though only one exists.

I am not optimising for price, but I am not indifferent to it either.

Which axes does this decision turn on?

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askedjonas_ekstrom12k3824 Aug 2024
5What syringe are you using? The answer is different for a 0.3 mL barrel and a 1 mL one. – plate_count_9k 9 months ago
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5 Answers

Accepted answer first, then by votes
99

Accepted answer

At 8 mg/mL a 0.25 mg draw is 3.1 units on a U-100 barrel and a 2.4 mg draw is 30. Those two numbers decide it, because the concentration is only sensible relative to the smallest and largest volumes you will actually measure with it. 3.1 units is too little of the scale to read honestly — half a graduation is 16 per cent of that dose — so going lower in concentration buys resolution you cannot get back after reconstitution. The other consideration is time: a vial you will finish in a fortnight can be concentrated, and a vial you will draw from for months should be split at reconstitution instead.

The honest answer is that a wide range of volumes works and that the extremes at either end cause avoidable problems.

Content matters. If the same 10 mg vial assays at 94 per cent content, you have 9.4 mg. In 2 mL that is 4.7 mg/mL, and a nominal 0.5 mg draw of 10 units actually delivers 0.47 mg — a six per cent shortfall that no amount of careful drawing will fix.

Round to a diluent volume you can measure accurately. Measuring 1.00 mL on a 1 mL syringe is reliable; measuring 1.37 mL on anything is not, and the error propagates into every dose.

U-100 means 100 units per millilitre by definition, so 1 unit is 0.01 mL and volume in millilitres times one hundred gives units. Every conversion here reduces to that.

The caveat is that this arithmetic assumes the vial contains what the label says, and without a content assay it is precise about an unknown quantity.

Choose the volume that puts your largest intended dose between 10 and 30 units. Everything else follows.

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answered · acceptedv_ramaswamy68k572 Nov 2024
Same experience here, different supplier. – Dr_Marek_Zielinski 5 months ago
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40

Total vial volume is a physical constraint: most 2 mL vials will not take 3 mL of anything.

For a dose that will change during titration, choose the volume for the largest intended dose rather than the first, so the whole schedule fits on one barrel without a mid-vial recalculation.

Write the concentration and the resulting units-per-dose on the vial label at reconstitution. The arithmetic that is obvious now will not be obvious at six in the morning three weeks from now.

Published content assay results across the independent testing services show nominal and measured content differing by one to ten per cent, which makes content the dominant term in dose error.

Concentration equals content over volume, and content is not label claim.

edited 7 Nov 2024 by Dr_Rosalind_Achebe — added a caveat about sampling

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answeredDr_Rosalind_Achebe69k14722 Oct 2024
7I have added the label-the-vial suggestion to my own notes. Obvious in hindsight. – Dr_Nadia_Farsi 22 days ago
6Does this change at lower concentrations, or does adsorption start to dominate? – low_dead_space 9 months ago
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28

Answer first: diluent volume sets concentration and therefore resolution on the syringe barrel, and resolution is free at reconstitution and impossible to recover afterwards.

Worked example. A 10 mg vial reconstituted with 2 mL gives 5 mg/mL. A 0.5 mg dose is 0.5 ÷ 5 = 0.1 mL, which on a U-100 syringe is 10 units. Reconstitute the same vial with 1 mL and the concentration doubles to 10 mg/mL, the same dose becomes 0.05 mL, and you are now reading 5 units instead of 10 — the same dose at half the resolution.

The other direction: 10 mg in 3 mL is 3.33 mg/mL, and a 0.5 mg dose becomes 0.15 mL, or 15 units. More barrel, easier reading, and a larger fraction of the vial volume lost to dead space across the same number of draws.

A concentration calculated to three decimal places from a diluent volume measured to one is false precision.

Measure a volume you can actually measure. Round numbers, real syringes.

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TN
answeredtabular_nums71k4811 Oct 2024
23

Start from the dose you intend to draw and work backwards to the volume that puts it in a readable part of the barrel.

Dead-space loss scales with the number of draws, not with the concentration, so a lower concentration spread over more draws loses proportionally less of the total peptide.

Nominal vial volumes in the standard 2R and 3R glass sizes have published brimful capacities well above the nominal fill, but the usable volume is bounded by the stopper displacement.

Nothing here is medical advice, and research-use material is not approved for human use.

Write the concentration on the label at reconstitution, in units per dose.

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DV
answeredDr_Bram_Verhoeven84k24830 Sept 2024
22

Aim for a dose volume somewhere between about 10 and 30 units on a U-100 barrel and the reading problem disappears.

Vial headspace is the hard constraint. A nominal 2 mL vial typically holds a little over 2 mL to the shoulder; adding 3 mL is not an option and attempting it wastes the lot.

Do not change the diluent volume between vials of a titration without recalculating; it is the commonest source of a ten-fold error.

Check the vial can physically hold the volume before you draw it up.

edited 9 Oct 2024 by tobias_maartens — added the placebo-arm figures

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answeredtobias_maartens171k35819 Sept 2024

Your answer

Ask PeptideStack is a static archive. Posting is closed, but the norms are worth stating: answer the question that was asked, show your working, cite the trial or the certificate, and say plainly where the evidence runs out.

Not medical advice. Research-use-only compounds are not approved for human use.