Thomas A. M. Kramer, MD


Medscape General Medicine. 2003;5(1) 

In This Article

Half-life and Steady State

One of the main reasons for this gets back to the issues of pharmacokinetics. To review some of the basics of pharmacology, medications vary in how long it takes to clear them from the body. Some are metabolized fairly quickly, while others can take a long time before they are eliminated. We quantify this with the use of the term "half-life." The half-life of a given medication is how long it takes for the body to get rid of half of the dose. When the patient is taking a medication on a regular basis, there is an ongoing process of drug absorption in the form of each dose of the drug and, concurrently, an ongoing process of drug removal with the drug's metabolism and clearance. Eventually, there comes a point when the amount of drug going in is the same as the amount of drug getting taken out. We call this "steady state." It takes somewhere between 5 and 6 half-lives for a medication to reach steady state. Thus, medications with short half-lives reach steady state relatively quickly, while those with long half-lives take a long time to reach steady state.

Many drug effects occur primarily when the blood level of the drug is either going up or going down. When the drug reaches steady state, these effects can be either attenuated or completely absent. For those of you who are familiar with calculus, one way to understand this is that these effects only take place if there is a first derivative other than zero. Unwanted side effects from a particular compound are great deal more acceptable if they only take place on the way to steady state (ie, they are transient). Another way to classify drug effects into 2 groups is to classify them into those effects that take place primarily while the blood level is changing and those effects that take place primarily when the blood level is stable at steady state. Ideally, for any drug, all of the unwanted effects would be in the former category and all of the therapeutic effects would be in the latter category. There are many examples of side effects of psychotropics that are considerably worse during increasing or decreasing blood levels of the medication. Extrapyramidal side effects from antipsychotic medications, gastrointestinal side effects from selective serotonergic reuptake inhibitors, and memory problems from benzodiazepines are some examples of this phenomenon.


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