Bioavailability

Bioavailability

Bioavailability is a basic pharmacokinetic measure: the fraction of a drug dose that reaches the bloodstream in active form. For drugs given into a vein, it is 100% by definition, because the whole dose enters the blood directly. For every other route, including by mouth, under the skin, into muscle or through the skin, it is usually below 100%. Some of the drug is not absorbed, is broken down by the liver on its first pass, or is degraded where it was given.

For peptide drugs like retatrutide, bioavailability drives decisions about formulation and route. Enzymes in the gut break peptides down quickly, which is why most GLP-1 receptor agonists, including retatrutide, are injected under the skin rather than swallowed. Injection under the skin gives peptides fairly high and consistent bioavailability, because absorption from the tissue into the blood is predictable and skips first-pass breakdown in the liver. That bioavailability sets the dosing regimen, since it decides what dose is needed to reach the target drug level in the blood.

Bioavailability also matters when comparing different forms of the same drug. Oral semaglutide, for example, has a bioavailability of only about 1% because the gut breaks most of it down, so the oral dose has to be much higher than the injected dose to reach the same blood levels. That is why injection is still the preferred route for most peptide drugs for metabolism, including retatrutide, where reliable delivery is needed to keep steady drug levels with once-weekly dosing.