Half-life.

The time for the amount of a compound in the body to fall by half.

Half-life is the time required for the concentration of a compound in the body to fall by 50%. It is the single most useful number for understanding why one peptide is a laboratory curiosity and another is a viable weekly drug. Native GLP-1, the hormone your gut releases after eating, is degraded so quickly by the enzyme DPP-4 that its half-life is measured in a couple of minutes, which makes the natural hormone useless as a medicine no matter how well it works. Semaglutide is the same signal re-engineered: amino-acid substitutions that block enzymatic cleavage plus a fatty-acid chain that binds albumin extend its half-life to roughly a week, which is what makes once-weekly administration possible. Similar strategies, including PEGylation and acylation, are used across the field. Half-life also governs how long it takes to reach a steady level and how long a compound lingers after the last dose, both of which run to several times the half-life. The misunderstanding worth correcting is equating half-life with duration of effect. A compound can clear from blood quickly while its downstream biological consequences persist, and the reverse is also true, so the two numbers are related but not the same.

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Compounds