The dog experiments
The percentage reaching blood has a chemical identity attached to it. The oral studies reward a closer look at which candidate made the journey.
An ipamorelin-derived series
In the series of orally active growth-hormone secretagogues, derivatives of the ipamorelin design achieved 10–55% oral bioavailability in dogs. A secretagogue stimulates hormone release. The same research program evaluated growth-hormone-releasing potency in rat pituitary cells and intravenously in swine.
Those are different experimental jobs. The dog measurements concern access to circulation after oral administration; the cell and swine tests concern a hormone response. I appreciate this division of labour. It leaves room to ask whether a structural change improves access, activity, or both, without assuming that one measurement answers everything.
An oral absorption measurement in a dog and an intravenous potency measurement in a pig describe different parts of development.
A second job for the stomach
A rat experiment with radiolabelled GHRP-6 and NN703 found that both compounds accumulated in the glandular stomach lining after intravenous administration. Gastric resection reduced the growth-hormone response to GHRP-6 by 60–70%, while the response to growth-hormone-releasing hormone was preserved. The resection result concerns GHRP-6.
The stomach had occupied a simple place in my imagination: an obstacle an oral candidate had to cross. This experiment gives it a more active role in the hormone story. The authors proposed that growth-hormone-releasing peptides partly act by triggering endogenous ghrelin secretion. It is a proposed mechanism from rat work, and NN703's presence in the tracer experiment deserves to stay separate from the GHRP-6 resection result.
NN703 in beagle dogs
The NN703 characterization reports 30% oral bioavailability and a plasma half-life of 4.1 ± 0.4 hours in beagle dogs. NN703 was structurally derived from ipamorelin for oral activity. That is an unusually concrete stop along the route: a named derivative, a species and a measurement of how long it remained in plasma.
I am satisfied calling that an absorption achievement. Extending the same satisfaction to lasting benefit would require another experiment. The cortisol finding in this characterization also gives the derivative a profile of its own.