# The Kinetics Table

> The Kinetics Table: Four Research Peptides Compared by Half-Life — Peptide Institute — Four research peptides side by side on pharmacokinetics: measured half-lives with the species and route attached, the chemistry each one uses to buy time, and why a duration figure is not a schedule.

**CROSS-COMPOUND / KINETICS**

Two orders of magnitude separate the shortest measured half-life here from the longest. The receptor is not what explains the gap.

## The short version

Four peptides. Two act on the pituitary through the growth-hormone-releasing hormone receptor, one acts on the ghrelin receptor next door, and one acts on a gut-hormone receptor entirely elsewhere. Comparing how well they work would be meaningless, because they are not trying to do the same job.

What compares cleanly is duration. How long does each one stay in the blood, what chemistry keeps it there, and how long do its effects last afterwards.

Read that way, three patterns hold. Chemistry predicts duration far better than molecule size does. The number always belongs to a species and a route, and moving it to another species or another route is not allowed. And the length of an effect is a separate measurement from the length of the exposure, sometimes off by weeks.

The tables below compress what the four compound pages say. Every figure in them is drawn from a cited study on the page it belongs to.

## The half-life table

Every entry names the species the figure was measured in and the route it was given by. Where the reference set holds no half-life figure, the cell says so instead of borrowing one.

| Compound | Duration figure in this reference set | Species and route | Source |
|---|---|---|---|
| CJC-1295, DAC form | Estimated half-life 5.8 to 8.1 days | Healthy adults, single subcutaneous dose | [4] |
| CJC-1295, preclinical conjugate | Peptide detectable in plasma beyond 72 hours | Rats | [7] |
| Ipamorelin | Terminal half-life approximately 2 hours | Healthy male volunteers, 15-minute intravenous infusions | [11] |
| Semaglutide | No half-life figure in this reference set; outcome trials administered it once weekly | Adults, subcutaneous injection | [14][15][16] |
| Tesamorelin | No half-life figure in this reference set; trials administered 2 mg once daily | Adults, subcutaneous injection | [20][21][22] |

Two of the four cells are refusals, and that is deliberate. Published half-life figures for semaglutide and tesamorelin exist, and both are easy to find. They are not among these 22 sources, so attaching them to a citation that does not carry them would be worse than leaving them out.

## Four ways to survive a protease

Peptide half-life extension solves two separate problems. Enzymes cut peptide bonds, and kidneys filter small molecules out of blood. A modification that answers one does not answer the other.

| Compound | Modification | What it defeats |
|---|---|---|
| CJC-1295 | D-alanine at position 2 plus substitutions at 8, 15 and 27; DAC form adds a maleimidopropionyl linker | Enzymatic cleavage, then renal filtration by covalent conjugation to serum albumin |
| Ipamorelin | Alpha-aminoisobutyric acid at position 1; D-2-naphthylalanine and D-phenylalanine | Enzymatic cleavage only |
| Semaglutide | Alpha-aminoisobutyric acid at position 8; arginine at 34; C18 fatty di-acid acylated onto lysine 26 | DPP-4 cleavage, then renal filtration by reversible albumin binding |
| Tesamorelin | trans-3-hexenoyl group at the N-terminus | DPP-IV cleavage only |

The pattern is legible. The two compounds that answer both problems are the two with the longest exposure: CJC-1295 at an estimated 5.8 to 8.1 days in healthy adults [4], and semaglutide, whose trials ran on a weekly injection [14][15][16]. The two that answer only the first clear fast — ipamorelin at about 2 hours in healthy male volunteers [11], and tesamorelin, whose brief plasma residence is the premise of its whole page.

A third strategy exists in the wider field and is worth naming for completeness. PEGylation attaches polyethylene glycol chains to increase a molecule's hydrodynamic radius, putting it above the threshold at which the glomerulus filters freely. None of the four compounds here uses it, and no PEGylated analogue appears in this reference set, so it is named rather than quantified.

## Route changes the number

A half-life is not a property of a molecule alone. It is a property of a molecule measured a particular way, and the route of administration is part of the measurement.

Ipamorelin's approximately 2-hour terminal half-life was measured after 15-minute intravenous infusions [11]. Intravenous dosing puts the entire amount into the circulation at once, so the disappearance curve reflects elimination and nothing else.

Subcutaneous injection behaves differently. The molecule has to be absorbed from the tissue first, and when absorption is slower than elimination the observed curve is governed by absorption rather than by clearance. A compound can appear far longer-lived subcutaneously without the body eliminating it any more slowly. Every other duration figure on this desk — CJC-1295's 5.8 to 8.1 days [4], the semaglutide trial schedule [14][15][16], the tesamorelin trial schedule [20][21][22] — comes from subcutaneous administration.

So the comparison in the first table is not quite apples to apples, and saying so is part of reading it honestly. Ipamorelin's number is an intravenous number sitting in a column of subcutaneous ones.

## Species changes the number too

The animal is part of the measurement in the same way the route is. Protease expression, renal function, albumin concentration and body composition all differ between species, and every one of them moves a pharmacokinetic parameter.

This desk cites work in four species. Humans: the CJC-1295 pharmacokinetic and pulsatility studies [4][5], the CJC-1295 proteomic study [3], the ipamorelin PK/PD and Phase 2 studies [10][11], every semaglutide trial [13][14][15][16][17], and every tesamorelin trial [18][20][21][22]. Rats: the CJC-1295 albumin-conjugate screen [7], the ipamorelin longitudinal bone-growth study [12], and the myocardial-toxicity study of a related GHS-R1a agonist [9]. Mice: the GHRH-knockout dosing-interval experiment [6]. Ferrets: the cisplatin weight-loss and emesis study [8].

The mouse study is the one most likely to be misread. In GHRH-knockout mice, 2 micrograms of CJC-1295 every 24 hours normalised body weight and length while dosing every 48 to 72 hours was progressively less effective [6]. That result is about what a knockout mouse needed to grow. It is not a human interval, it does not scale into one, and the fact that it looks like a schedule is precisely why it needs the species stamped on it.

## The exposure curve and the effect curve are different curves

The most consistent finding across these four compounds is that duration of exposure and duration of effect are separate quantities, measured separately, and frequently far apart.

CJC-1295 has an estimated half-life of 5.8 to 8.1 days in healthy adults, yet IGF-1 remained above baseline for up to 28 days after multiple doses [4] — several half-lives past the last injection. Ipamorelin clears in about 2 hours, and its growth-hormone response is a single pulse peaking at roughly 40 minutes [11]: effect shorter than exposure, not longer. Tesamorelin clears quickly and holds a 18 per cent reduction in visceral adipose tissue across 52 weeks [22], which reverses when dosing stops [22]. Semaglutide, on weekly administration, produced a -14.9 per cent mean body-weight change over 68 weeks [16] — an effect measured in months on a molecule dosed in weeks.

Four compounds, four different relationships between the two curves. Any rule of thumb that converts a half-life into a schedule has to hold across all four, and none does.

## What this table does not tell a reader

It does not rank these compounds. A half-life is not a merit score, and a longer one is not better — it is a different set of tradeoffs, including a longer interval during which an adverse effect cannot be withdrawn.

It does not compare their evidence. On that axis the four are not close: semaglutide carries randomised outcome trials enrolling 17,604 [15] and 3,533 [14] participants; tesamorelin carries a five-trial meta-analysis [18] and an approval [19]; ipamorelin carries one Phase 2 trial that missed its endpoint [10]; CJC-1295 carries early pharmacology studies in small numbers of healthy volunteers [4][5] and no approval anywhere [4].

It does not compare their safety, which lives on the individual pages and is not commensurable across three receptor families.

And it does not produce a dosing interval for anybody. Trial protocols are reported here as facts about trials. Turning a measured half-life into an interval requires an indication, a population, a target exposure and a monitoring plan — the work of a prescriber, and out of scope for a literature desk.

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Peptide Institute is a reading desk and not an institute: it reports pharmacokinetics measured by other people, names the species behind every number, and prescribes nothing to anyone.