Bioavailability is the fraction of an administered dose that reaches systemic circulation intact. Intravenous is 100 percent by definition. Everything else is a discount, and the size of the discount varies from small to enormous depending on route and molecule.

For peptides the discount is usually large, because peptides are exactly the kind of molecule biology is built to destroy: charged, water-soluble, too big to cross membranes passively, and made of the bonds that every protease in your body exists to cleave.

Subcutaneous injection

Inject into the fat layer under the skin and the peptide sits in the interstitial space, then moves into capillaries or, for larger molecules, into lymphatic vessels and eventually to the thoracic duct. Absorption is slower than intramuscular, which is often desirable, and the first pass through the liver is bypassed entirely.

Typical subcutaneous bioavailability for peptides runs 60 to 90 percent, with smaller peptides at the higher end because they enter capillaries directly rather than depending on lymphatic uptake. Semaglutide subcutaneous bioavailability is approximately 89 percent. Insulin analogues sit in a similar band. Losses come from local proteolysis in the subcutaneous tissue and from injection technique.

The variables you control: needle length and angle (a 4 to 8 mm needle at 90 degrees into a pinched fold is the standard for subcutaneous, longer needles risk intramuscular delivery, which changes the absorption curve), site rotation (repeated injection at the same site produces lipohypertrophy, and absorption through hypertrophied tissue is erratic and reduced), and injection speed.

Intranasal

The nasal route is attractive on paper. Rich vascular supply, thin epithelium, no first pass metabolism, and no needle. The reality is harsher.

Bioavailability for peptides intranasally is typically 0.5 to 5 percent without a permeation enhancer, and 10 to 20 percent with one. Three barriers explain this. Mucociliary clearance sweeps the sprayed dose toward the pharynx in about 15 to 20 minutes, so most of what you spray gets swallowed and digested. The nasal epithelium has tight junctions that molecules above roughly 1000 daltons cross poorly. And the mucosa itself is rich in aminopeptidases.

Two things follow. First, an intranasal product needs a dose maybe 20 to 50 times higher than the injectable equivalent to deliver comparable systemic exposure, which is why nasal products that work commercially (desmopressin, calcitonin, oxytocin) are either very potent at low absolute doses or accept low bioavailability by design. Second, variability is dreadful. A cold, allergic rhinitis, a deviated septum, spraying with the head at the wrong angle, or sniffing hard after actuation (which drags the dose to the back of the throat) can each move absorption by a large factor. Reproducibility between days, in the same person, is poor.

There is one genuinely interesting exception, which is direct nose-to-brain transport along the olfactory and trigeminal nerve pathways. Intranasal insulin studies for cognition are built on this, and the mechanism appears real, but it delivers to the central nervous system rather than to the periphery, so it does not rescue a peptide meant to act on muscle or fat.

Oral, briefly

Oral peptide bioavailability without engineering is well under 1 percent. Oral semaglutide gets to roughly 0.4 to 1 percent using SNAC, an absorption enhancer that locally raises gastric pH and promotes transcellular uptake, and it requires dosing fasted with no more than 120 ml of water and a 30 minute wait before anything else. That is what it takes to make an oral peptide work, and it is why almost no other peptide is sold that way. Any product claiming meaningful oral absorption of a peptide without that kind of formulation science behind it is not doing what it says.

Pre-filled pens versus vial and syringe

This is not a bioavailability question, both deliver subcutaneously and absorb the same. It is a dose accuracy and handling question.

  • Pens deliver a metered dose by dial. Studies of insulin pen versus syringe accuracy consistently favour pens, particularly at small volumes where syringe reading error is proportionally largest. Pens also reduce contamination risk since the cartridge is never opened.
  • Vial and syringe requires you to reconstitute lyophilised powder yourself and read a volume off a barrel. At the doses common in peptide use, you are often drawing 5 to 20 units on an insulin syringe, where a half-unit misread is a 5 percent dose error. Reading error, air bubbles, and dead space in the hub all contribute.
  • Dead space is worth naming. A standard needle hub retains 50 to 100 microlitres. On a 100 microlitre dose that is a large proportion lost. Low dead space syringes with the needle fixed to the barrel reduce this to a few microlitres.

The practical summary

Subcutaneous injection with a low dead space insulin syringe or a pen is the route with the best combination of absorption and reproducibility, which is why essentially every peptide with real clinical evidence behind it was studied that way. Nasal delivery trades a large and unpredictable amount of your dose for the convenience of not injecting, and if a supplier sells a nasal version at the same milligram figure as the injectable version, the two are not equivalent products.

Where the evidence stops: most compounded or grey market nasal peptide products have no published bioavailability data at all. Nobody has run the pharmacokinetic study. Estimates in this article come from the general peptide nasal delivery literature and from the specific approved products, and applying them to an untested formulation is inference rather than measurement.