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
It’s because in a lot of cases, people who take them _are_ dosed ~6 times a day.
Inside the big capsule is a lot of little balls of medication, all of them dissolving at different rates. Think of them like a bunch of little jawbreakers, all of them different sizes, and the core of each is the medication. As the day goes on, the shells of the jawbreakers slowly get worn away, letting your body access another bit of medication every few hours. That way you only need to take one pill at the beginning of the day instead of taking a whole bunch.
You’re missing a huge piece of the puzzle, which is active metabolites. Active metabolites are metabolic byproducts of a drug that continue to to produce the effects of the drug even after the parent drug has been metabolized. Active metabolites can not only have half-lives much longer than the parent drug, but can also be more potent than the parent drug itself.
To use your example of buspirone, it has several active metabolites. The main ones are 5-hydroxybuspirone, 6-hydroxybuspirone, 8-hydroxybuspirone, and 1-(2-pyrimidinyl)piperazine.
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
I heard some pills are designed to release the active drug at a controlled rate. Which apparently is why two brands with the same drug and dose may work differently.
There is also delayed release pills. They are coated to survive your stomach and then slowly break down over a longer time period in the gut. This is the reason some medications say not to crush or chew since that would drastically change how/if your body absorbs it, and it is why things like rapid release liquid gel tablets exist.
Latest Answers