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Margin of Safety in Pharmacology: Definition & Formula

Instructor: Artem Cheprasov

Artem has a doctor of veterinary medicine degree.

This lesson defines and explains the margin of safety and the therapeutic index. Then it shows you the formula for the therapeutic index and showcases some advanced considerations with respect to this topic.

Margin Of Safety

Pretend you're a doctor. As a doctor, you have two main goals: treat the patient and avoid doing harm to the patient at the same time. So when you give your patient a drug, you want to give it at a dose that is above an ineffective level, but below a toxic level. This range of doses is referred to as the margin of safety of a drug. The margin of safety of a drug is a concept that tells us how safely we can use a drug for therapeutic purposes without risking too many adverse effects at the same time.

Let's learn more about this topic.

Formula

The margin of safety is estimated by something known as the therapeutic index (TI). The TI uses two important concepts in one equation that denotes the margin of safety of a drug. These concepts are known as the ED50 or the effective (therapeutic) dose in 50% of people and the LD50, which is the lethal dose in 50% of people.

The therapeutic index (TI) is given by a number that is computed very simply as follows:

TI = LD50/ED50

As a quick side-note: a similar 'clinical' therapeutic index exists. Here, TD50, or toxic dose 50%, is used instead of LD50 in the formula above. The LD50 is actually an extrapolation of animal data onto humans. Thus, human (and some animal) based studies find TD50 not LD50. With TD50, we're not just concerned about lethality but also any (even minor) adverse effect. While the mechanisms that cause toxicity are not necessarily the same ones that cause lethality as a result of a drug, we'll stick to using LD50 in this lesson as a measure of non-lethal and lethal toxicity (adverse effects) for simplicity's sake.

Basic Concepts

Given that, there are some important general things to consider and remember with respect to the TI and thus margin of safety of a drug:

First, the closer the ratio is to 1, the greater the chances of one or more adverse effect.

Second, drugs that have a low TI have a narrow margin of safety. This means they are relatively risky. It also means that drug's plasma (serum) levels need to be watched carefully and the person's signs and symptoms carefully monitored for any adverse reactions.

Lastly, drugs that have a high TI, have a wide margin of safety. This means they are relatively safe and the drug's levels in the blood typically don't need to be monitored for. In other words, a larger value for our TI tells us there is a wide margin (of safety) between the doses of a drug that are effective vs. the doses of the same drug that are toxic.

What you should've gathered by now is that we want the effective dose to be much smaller than the lethal dose. Think of it this way. If the ED50 is really low and the LD50 is really high, a person would need to take a huge dose to experience serious adverse effects. Compared to this latter example, if the ED50 is really high and the LD50 is really low, then the person may experience serious detrimental effects by taking just a teeny-tiny bit more than they were prescribed. In other words, an accidental overdose can prove easily deadly in the latter scenario.

Advanced Topics

What you've just learned about the margin of safety is just the simple but very important view of things regarding this topic. There are many other considerations with respect to the therapeutic index and thus the margin of safety that play a role in deciding which drug to use and when. This lesson cannot cover all of them in any great detail, but they are here for your quick consideration nonetheless:

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