Pharmacokinetics
The study of how the body processes a drug over time, encompassing absorption, distribution, metabolism, and excretion (ADME). Peptides face unique pharmacokinetic challenges including poor oral bioavailability, rapid proteolytic degradation, and primarily renal clearance.
Technical Context
PK properties are described by the ADME framework. Absorption: subcutaneous bioavailability is typically 60-90%, oral peptide bioavailability is usually <1-2% (oral semaglutide ~0.4-1%). Distribution: most peptides distribute primarily in extracellular fluid with small Vd (0.1-0.3 L/kg); albumin-bound peptides have distribution limited by albumin's distribution. Metabolism: unlike small molecules metabolised by hepatic CYP450 enzymes, peptides are degraded by ubiquitous tissue and plasma proteases, reducing drug interaction risk. Excretion: peptide fragments are filtered by kidneys; intact larger peptides and albumin-bound peptides are filtered less efficiently. Key PK parameters include Cmax, Tmax, AUC, half-life (t1/2), clearance (CL), and volume of distribution (Vd).