Bioavailability

The regulatory definition

21 CFR 314.3, which also governs bioavailability terms in part 320, defines bioavailability as the rate and extent to which the active ingredient or active moiety is absorbed from a drug product and becomes available at the site of drug action. For products not intended to be absorbed into the bloodstream, the regulation allows assessment by measurements that reflect availability at the site of action. The definition is about a drug product, not about a nickname on a research vial.

Two words carry the definition: rate and extent. How fast the active moiety arrives, and how much of it arrives. A claim that a peptide is "bioavailable" with neither a route nor a fraction is not using the regulatory meaning.

What changes it for peptides and proteins

Richter and Jacobsen describe the subcutaneous case for biotherapeutics. Absorption is relatively slow and mostly incomplete. Transport through the subcutis to blood or lymph capillaries is a major reason it is slow. Larger proteins, above about 20 kDa, are mostly absorbed via lymph. Presystemic catabolism contributes to the incomplete extent. [1] PMID: 25100673

That is bioavailability as a number you could, in principle, measure: the fraction of the administered active moiety that becomes available, and the time course of that availability. It is not the same number as half-life. Toutain and Bousquet-Mélou separate the terminal plasma half-life from the time required to eliminate half the dose, and they note that when absorption limits the profile, the terminal half-life reflects absorption rather than elimination. [2] PMID: 15601438 Quoting a half-life and calling it bioavailability mixes the two.

What the word is not

It is not oral absorption by default. Many peptides are discussed as injections precisely because the gut destroys them. It is not a purity assay. A 99% HPLC figure says something about what is in the vial. It says nothing about the fraction that reaches the site of action after a given route. It is not reconstitution. Dissolving a cake makes a solution. It does not determine the rate and extent of absorption of that solution.

It is also not a license to compare a subcutaneous research peptide with an intravenous approved drug and declare them equivalent. Bioequivalence, in the same CFR section, is the absence of a significant difference in rate and extent between products under the conditions of an appropriately designed study. A forum comparison is not that study.

How this site should cite it

Administration and dosing guides are where route and exposure show up. This entry is the definition they should link. If a compound page says a peptide has "high bioavailability," the sentence needs a route, a species, and a source. Without those, the FDA definition has not been met, and the sentence should not be written.