Why is steady state important

This can also be extended to different dose levels if you assume dose proportionality. The time to reach steady state is defined by the elimination half-life of the drug.

If you have a drug with a long half life, you can achieve a target steady state level more quickly by using a loading dose. However, it will take 10 days to achieve steady state. Therefore you could achieve the target C ss more quickly by administering one 60 mg dose followed by 30 mg doses to achieve steady state levels within 2 days. The 60 mg dose is called a loading dose , and the 30 mg dose is the maintenance dose or dose to maintain steady state.

Steady state pharmacokinetics are important for chronically administered drug products. Understanding the basic concept that a drug reaches steady state once the rate of drug input and elimination are equivalent helps simplify the concept of steady state. Hopefully you have a clearer understanding of steady state and can utilize this information in your upcoming projects.

Featured Product. Simcyp: 20 Years of Innovation. Certara Appoints James E. Contact Investors Careers Support. Mon, November 25th Knowledge Base. Contact Us. PK parameters associated with steady state There are several special PK parameters associated with steady state kinetics. The situation is even simpler for intravenously administered drugs where you can directly calculate the C ss using the following equation: where R 0 is the rate of drug input. The C ss is proportional to the infusion rate directly.

To be effective the drug must reach a certain level and so must our water in the bucket but the body is not a closed system and the drug can be lost by being broken down in the liver and excreted from the kidneys. This loss of drug from the body can be represented by putting a small hole in the bucket so that some water is constantly leaking out.

Like the drug level in the body, the level of water drops and needs to be topped up by giving regular doses. If a single dose is given every half-life, half of the first dose will be cleared from the body before the next dose.

So, after the second dose, there will be 1. Half of that is eliminated and then the next dose is given, meaning there are now 1.

At dose 5 after five half-lives , there will be close to two doses in the body, which means one entire dose is eliminated each dosing interval. If we continue dosing at the same frequency, the amount we dose will be eliminated during each dosing interval.

As a result, drug concentrations in the body remain constant steady. Another way to think about steady state:. But a very simple way to remember it is that the average C ss is the total exposure AUC over one dosing interval divided by the duration of the dosing interval.

For a drug with a short half-life, steady state is achieved pretty quickly. If you have a drug with a long half-life and a patient who needs to achieve a therapeutic effect fast—for example, a critical care patient who needs antibiotics—how can you get that effect without having to wait days or weeks?

The bad news is that it always takes the same amount of time to achieve steady state: Four to five half-lives. The good news is, you can still achieve a therapeutic effect more quickly with a loading dose.

A loading dose is a higher dose administered on treatment initiation. It will still take the usual four to five half-lives to reach steady state, but the initial concentration will be closer to the eventual steady-state concentration—which means the therapeutic effect will happen faster.