Half-Life
Definition
The time taken for the amount in the body to fall by half. It sets how often a compound has to be given and how long elimination takes, about four to five half-lives for the bulk of it to clear.
In more detail
Half-life is the time taken for a concentration to fall by half. Because the same fraction is lost over each interval rather than the same amount, the decline is exponential and the absolute drop gets smaller as the concentration does.
It is a property of the molecule in a particular system rather than of the molecule alone. The figure measured in plasma, in buffer at a bench, and in a cell culture experiment can differ by orders of magnitude, so a half-life quoted without the system it was measured in is not a number anything can be done with.
For peptides it is the property most often engineered. Acylation, PEGylation, backbone modification and fusion to a carrier protein are all ways of extending it, mostly by slowing clearance or by binding the molecule to something that circulates for longer.
Where this term comes up
Entries whose definition mentions Half-Life.
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
Clearance
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.
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 clearance 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 parenteral routes, which bypass the gut.
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.
