How can medications with very short half lives (~2 hours) ever be effective given that a non-negligible steady state is never achieved unless dosed like 6 times/day?

Question

There are some medications, like buspirone, that have a very short half-life of 2-3 hours. Even if you took it twice a day, you’d only end up achieving a steady state of about 3-5% of the original dose. It’s very easy to do the math on Excel: [here’s an example of a 2 hour half-life medication taken twice a day](https://i.imgur.com/2N7HbmT.png).

One possible solution is taking the medication a ridiculous number of times per day, which is simply not going to happen (it’s hard enough to get daily compliance out of patients).

A second possible solution is prescribing a dose that’s like 10-50x larger than the desired steady-state level. For example, let’s say taking 100mg (2x/daily) of a medication provides a steady state of about 1-3% of that dose (as is approximately the case for a 2x/daily medication with a ~2 hour half life). If the *desired* steady state is 75% of that dose, you could achieve that steady-state by instead prescribing **2500mg** 2x/daily.

The problem with that, I assume, is that a 25x larger dose of almost *any* medication would have intolerable side effects.

But obviously these medications are approved, prescribed, used, and apparently actually do work. **But how?** I just don’t see how it’s possible. I’m sure I’m just missing something.

In: Biology

Answer 1

Not all medications require to reach steady state to exhibit the effect we want them to. Achieving steady state is important when you want a constant concentration of a drug in the body. But that’s not always necessary. Short half life can be an advantage for some treatments. Buspirone is a good example. It’s used for short-term treatment of anxiety. It has a fast onset of action to calm someone down for a few hours and it will not stay in the system for long which minimises its side effects. It’s for people who need treatment to manage acute anxiety attacks. Once it helps to manage that they’ll go back to their baseline state and not require treatment until another onset. If someone requires a drug with longer duration of action then a drug with a longer half life is likely to be a better option