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Pharmacokinetics describes what the body does to the drug through the ADME cycle.
- Absorption. The oral route is hostile to almost all peptides: gastric and intestinal proteases degrade them and their size/polarity limits transmucosal passage. That is why the parenteral (subcutaneous) route predominates. Bioavailability quantifies the fraction that reaches the systemic circulation intact.
- Distribution. The volume of distribution (Vd) reflects how much the drug spreads into tissues versus staying in plasma. Binding to plasma proteins (albumin) can create a circulating reservoir.
- Metabolism. Peptidases in plasma, kidney and liver hydrolyze peptide bonds. DPP-4 is the paradigm, trimming incretins within minutes.
- Excretion. Low-weight fragments are eliminated mainly by the renal route; kidney function is therefore a relevant pharmacokinetic variable.
Time parameters
The concentration-time curve is summarized by: Cmax (maximum concentration), Tmax (time to Cmax), AUC (area under the curve, total exposure), clearance (CL) (volume cleared per unit of time) and half-life (t½) (time to halve the concentration). The t½ determines the dosing frequency and the time to steady state (~4-5 half-lives).
Native GLP-1 has a t½ of ~1-2 min because of DPP-4. Semaglutide reaches ~1 week. That jump is no accident: it is the direct result of the molecular modifications described below.
Catalogue compounds mentioned in this lesson
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