Bioavailability

Bioavailability is the share of a dose that reaches the general circulation intact. An intravenous dose is 100 percent bioavailable by definition, because it goes straight into the blood. Every other route loses something on the way: to digestion, to enzymes in the tissue, to the liver before the drug reaches the rest of the body, or simply to incomplete absorption.

"Absolute bioavailability" compares a route with an intravenous dose of the same drug. It is measured by giving both and comparing the area under the concentration curve, the AUC described on the pharmacokinetics page.

The GLP-1 numbers

Injected under the skin, most of the semaglutide dose arrives. Swallowed, almost none of it does. That is why the oral doses are so much larger than the injected ones: 25 mg a day by mouth against 2.4 mg a week by injection for weight management. The labels report similar average steady-state concentrations for the two, about 77 nmol/L on the 25 mg tablet and about 75 nmol/L on the 2.4 mg injection, which is the point of the dose difference.

Why peptides are hard to swallow

The stomach and gut are built to break proteins and peptides into amino acids. A peptide drug is food as far as digestion is concerned. Oral semaglutide gets through by being co-formulated with an absorption enhancer, salcaprozate sodium (SNAC), and the label says absorption happens mainly in the stomach. The conditions are strict for the same reason: take it on an empty stomach with up to 4 ounces of water and wait at least 30 minutes before eating, drinking or taking other tablets. The Rybelsus label reports that absorption was higher with 50 mL of water than with 240 mL.

Orforglipron (Foundayo) takes a different route. It is a small molecule rather than a peptide, so digestion does not destroy it. The Foundayo guide and oral Wegovy guide cover each.

Low bioavailability means high variability

When only 1 percent of a dose gets in, a small change in conditions is a large change in exposure. A tablet taken with coffee, or with a full glass of water, or ten minutes before breakfast, can absorb noticeably less. The injected forms are far less sensitive. For research peptides sold as capsules or nasal sprays, absorption figures are usually missing altogether, which means the dose on the label says little about the dose in the blood.

If you take an oral GLP-1, the dose log can record the time of the tablet and the time of the first meal, so a pattern of short waits shows up next to weight and side effects instead of being guessed at.

Related terms: pharmacokinetics, half-life, steady state, peptide bond. Back to the glossary.