Clearance (Pharmacology)
The volume of blood from which a drug is completely removed per unit of time, reflecting the body's efficiency at eliminating the drug. For peptide drugs, clearance occurs primarily through proteolytic degradation by tissue and plasma enzymes and through renal filtration of smaller peptide fragments.
Technical Context
Clearance (CL) reflects the body's overall ability to eliminate a drug: CL = Dose/AUC. For small peptides (<5 kDa), renal filtration is the dominant clearance mechanism, with glomerular filtration rates of approximately 120 mL/min. Larger peptides and albumin-bound peptides are cleared more slowly because they are not efficiently filtered. Proteolytic degradation by tissue and plasma enzymes contributes to clearance at all molecular weights. Unlike small molecule drugs, peptides are generally not metabolised by hepatic CYP450 enzymes, which means peptide drugs have a lower propensity for metabolic drug-drug interactions. Clearance determines maintenance dose requirements: Dose rate at steady state = CL × target Css.