Steady state

The point where the amount of a compound going in equals the amount clearing out, so the average concentration stops rising. It takes about five half-lives to get there.

Glossary 6 min read Editorial policy

Steady state is the equilibrium a repeated dose eventually reaches. Take a dose before the previous one has cleared and concentration builds. It keeps building, but by less each time, until the amount eliminated between doses equals the amount administered. From then on the level oscillates around a stable average instead of climbing.

It is the single most useful idea for interpreting what a compound is doing, because almost every judgment people make about whether something is working is made before it arrives.

Five half-lives, and why that number

The approach is exponential, which means it is predictable and independent of the dose. After one half-life you are at 50 percent of the eventual steady-state average, after two 75, after three 87.5, after four roughly 94, after five roughly 97.

Five half-lives is the working convention because 97 percent is close enough that the remaining climb is not clinically meaningful. The same arithmetic runs in reverse on stopping: five half-lives later, roughly 97 percent has cleared.

The dose does not change how long this takes. A larger dose reaches a higher steady state, not a faster one. Frequency does not change it either. Only the half-life does.

A bigger dose gets you to a higher plateau. It does not get you there sooner.

Why this changes how you read your own results

For a compound with a one-week half-life, steady state is roughly five weeks away. Assessing whether it is doing anything at week two means assessing a concentration still well below where it will settle, and concluding it does not work is a conclusion about the wrong level.

The same applies to side effects, in the opposite direction. Effects that appear early can reflect a rising concentration rather than a stable one, which is part of why titration schedules exist and why holding at a step is a normal response.

It also matters for bloodwork. A level drawn before steady state is not comparable to one drawn after, and neither is comparable to one drawn at a different point in the dosing interval. Trough, the point immediately before the next dose, is the conventional sampling point precisely because it is reproducible.

Peak, trough, and the size of the swing

Steady state is an average, not a flat line. Within each interval concentration still rises after a dose and falls before the next. How large that swing is depends on the interval relative to the half-life.

Dosing frequently relative to half-life produces a small swing and a nearly flat curve. Dosing at intervals long relative to half-life produces large peaks and deep troughs, and the compound may spend part of each cycle below the concentration where anything happens. This is why dosing frequency is not simply a convenience question.

The half-life calculator reports the accumulation ratio and how much remains at the next dose, which is the swing expressed as numbers.

What a loading dose does

A loading dose is the one way around the five-half-life wait. A larger first dose fills the volume the compound distributes into, so the concentration starts near where maintenance dosing will hold it rather than climbing from zero.

It changes the time to reach the level. It does not change the level itself, which is still set by the maintenance dose and the clearance. And it front-loads exposure, which is the trade: whatever the compound does at that concentration, including the unwanted parts, arrives immediately rather than gradually. For compounds where the ramp exists to build tolerance, a loading dose defeats the purpose.

When you cannot calculate it at all

All of the above needs a half-life, and for most research peptides there is not a reliable one. Where a figure circulates it is often from an animal model, from a single small study, or from a route other than the one being used. Extrapolating a mouse half-life to a human dosing interval is not arithmetic, it is a guess wearing arithmetic's clothes.

The honest position for those compounds is that time to steady state is unknown, which also means the interval at which they are dosed is convention rather than calculation. That is worth knowing before treating a protocol's schedule as though it encodes something. Every compound page on this site grades how much research sits behind the compound, and for a large share of them the answer is very little.

Related terms: half-life, titration, loading phase, pharmacokinetics.

Keep reading

Open the half-life calculator

57 peptides, each labelled with how much research is behind it, including the ones where the answer is very little.

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