First-pass metabolism
The metabolism of an orally administered peptide by the gut wall and liver before it reaches systemic circulation. First-pass effect dramatically reduces oral bioavailability for most peptides.
Frequently Asked Questions
What is First-pass metabolism?
Why is First-pass metabolism important in peptide research?
Related Terms
The fraction of an administered dose that reaches systemic circulation unchanged. Subcutaneous injection provides 65–95% bioavailability for most peptides; oral bioavailability is typically below 1% without absorption enhancers.
Hepatic metabolismThe breakdown of peptides by liver enzymes. Most peptides are degraded by proteases rather than CYP450 enzymes, which means fewer drug-drug interactions compared to small-molecule drugs.
Oral administrationDelivery of a peptide by mouth in tablet or capsule form. Most peptides have poor oral bioavailability due to enzymatic degradation in the GI tract, though new formulations like oral semaglutide (Rybelsus) use absorption enhancers.
CYP450Cytochrome P450, a superfamily of liver enzymes responsible for metabolizing most small-molecule drugs. Peptides are primarily degraded by proteases, not CYP450, which reduces their drug interaction potential.