The Half-Life Rule of Five

If you prefer to listen to podcasts, feel free to play the audio version of this blog by clicking on the player above.

Podcast: The Half-Life Rule of Five
Length: 5 min 05 seconds
Written and read by the author

The time to Steady State cannot be altered. This means that dumping higher or more frequent doses does not shorten your time to steady state. It remains a relationship between the body and the drug’s half-life. To keep things simple, remember the Rule of Five: it takes five half-lives to reach steady state and functional elimination. So, if you take a drug’s half-life, say 9.6 hours, and multiply it by 5, then 48 hours is the time for both steady state and drug elimination. How is this possible? Well with steady state, you assume that we are dosing the patient at regular intervals going forward and for elimination, we have discontinued therapy. In this way, the timing gives us two landmark times depending upon the context of the situation.

So, what does that mean to you? Well, if you are taking a drug twice daily and it has a half-life of 9.6 hours, then it will take two days for your body to reach the plateau – the level that will be maintained going forward throughout your treatment period. After two days, you can assume that this will be how you will feel during the rest of your treatment course. On the other hand, let’s assume you are having an adverse effect from the drug so you stop the medication. How long will the drug be having functional effects on you? Again, two days – assuming all things are equal.

To be clear, the Rule of Five allows for an easy “down and dirty” calculation. For individual drugs, the Rule of Five provides a functional framework but by no means represents an absolute. Every drug differs. Speaking once again in generalities, most drugs take four to five half-lives to reach steady state and five to seven half-lives for functional elimination.

Often, we wonder how many doses we need to reach steady state. All you need to do is to multiply the half-life by five and then divide that time by the dosing frequency. It is easier than it may sound. Example 1: you take a drug twice daily. The half-life is 12 hours. 12 hours x 5 is 60 hours. Since you are taking the medication every 12 hours, then after 5 doses you will be at steady state. Another example? Your drug half-life is 10 days, but you only take the drug once a month. At 50 days, you reach steady state, a time just before your third dose. The first dose would be at day zero, the second at day 30 and the third would occur ten days after you reached steady state. Last example, you take a drug once a day and it has a short half-life of 4 hours. In this example, you will be at steady state by the time you take your second dose. Easy right?