Clearance
Definition
The rate at which the body removes a compound from blood, through the kidneys, the liver, or enzymatic breakdown in plasma. Clearance together with volume of distribution is what produces the half-life, rather than the other way round.
Terms used in this definition
Other entries this definition refers to.
What this means for research sourcing
Mechanistic terms like this describe how research compounds behave in vitro. See the mechanism overviews for compounds Volta stocks.
Related Terms in Pharmacology
Steady State
The point in repeated administration where the amount going in matches the amount being cleared, so peaks and troughs stop climbing. It takes roughly four to five half-lives to arrive, whatever the interval.
Area Under the Curve (AUC)
Total exposure over time, the integral of plasma concentration against time. Two regimens can share a peak concentration and differ substantially in AUC, which is why trials report both.
Pharmacokinetics
What the body does to a compound: absorption, distribution, metabolism and excretion. Half-life, peak concentration and dosing interval all come out of pharmacokinetic work.
Pharmacodynamics
What a compound does to the body: the link between concentration at the target and the size of the resulting effect. It is the counterpart to pharmacokinetics and the two are routinely modelled together.
First-Pass Metabolism
The breakdown a swallowed compound undergoes in the gut wall and the liver before it reaches general circulation. It is a principal reason peptide drug development has concentrated on injected routes.
Enzymatic Degradation
Cleavage of a peptide by proteases in blood and tissue, which cut at sequence-specific points. Designing around it, by substituting a residue, cyclising the chain or capping a terminus, is the central problem in making a natural peptide usable as a drug.
DPP-4 (Dipeptidyl Peptidase-4)
The enzyme that inactivates native GLP-1 and GIP within a couple of minutes of their release by clipping two residues off the N-terminus. Long-acting incretin analogues are engineered to resist it, which is what turns a minutes-long hormone into a weekly one.
Receptor Agonist
A molecule that binds a receptor and switches it on, producing the kind of response the endogenous signal produces. Most peptide drugs are agonists at a receptor their parent hormone already occupies.