Bioavailability (F) is the fraction of an administered amount that reaches systemic circulation chemically unchanged. Intravenous delivery is 100% by definition, and every other route is expressed relative to it, derived from the ratio of areas under the concentration-time curves. It is a measured quantity for a specific molecule, route and species, not a property that can be inferred from structure.
Why bioavailability matters in peptide research
Peptides are the hard case. They are large, charged and hydrophilic, so they cross membranes poorly, and the gut lumen is full of proteases that cleave them before absorption. Unassisted oral bioavailability for a typical peptide is commonly reported below 1%, which is why the oral semaglutide formulation relies on the absorption enhancer SNAC and still lands in the low single digits. Subcutaneous delivery in animal models usually recovers a large majority of the administered amount, while intranasal and sublingual routes fall between the two and vary widely with formulation.
For research design the number matters because comparisons across formats are only meaningful once route is accounted for. Amounts stated for an oral capsule format and an injectable vial are not equivalent inputs. Format trade-offs are set out in the oral peptides guide.