Medication Half-Life: What it Means and Why it Matters

Medication half-life: graphic of a capsule pouring into an hourglass

If you take meds, or even if you haven’t, you may have heard of medication half-life. But what does it actually mean? As a former pharmacist, that question is right up my alley.

Pharmacokinetics

Half-life has to do with pharmacokinetics, which refers to the way a drug moves through the body. There are four aspects to pharmacokinetics:

  • Absorption: how a drug enters the circulatory system
  • Distribution: how it moves into the places in the body where it hangs out
  • Metabolism: changes in the form of the drug before it’s excreted
  • Excretion: how it gets out of the body

After the drug is absorbed, it will reach a peak concentration in the plasma (the fluid part of the blood, not the cells floating around in it). Then that concentration will start to drop as the body starts to clear out the drug.

Half-life, or elimination half-life to be more specific, refers to the time it takes for the plasma concentration to drop to half of what it was at its peak.

Steady state

Steady state is a groove that your body gets into when taking a medication regularly. This means the maximum and minimum plasma concentrations of the drug in your blood are pretty much the same every day. After starting or changing the dose of a medication, it takes about 3-5 half-lives to reach steady state. That’s why you need to wait a few days after a change in your med dose before going to the lab.

A graph demonstrating plasma concentration and steady state
Wikipedia

This graph is an example of a medication that’s taken daily. You can completely ignore everything except the bright blue line. The blue line begins in the bottom left corner, where you have no drug at all in your system. You take your first dose, and the concentration shoots up (or goes up more slowly if it’s an extended-release formulation). When you take your next dose 24 hours later, you still have some drug kicking around in your system. After you pop the second dose, your maximum concentration reaches a higher level than it did after your first dose. The third dose goes up a little higher, and then the curve after the fourth dose looks just like the curve after your third dose. Boom, steady state.

Blood levels

The timing of when you take your medication and when you go for bloodwork reflects where they want you to be on that curve. If you increase your dose and go to the lab the next day, you won’t have reached steady state yet, so you’re not measuring the right thing. If you go for a blood level an hour after your dose, that’s going to give a very different number than the level 12 hours after the dose.

Ideally, a blood level would be drawn to correspond to a true trough (the lowest point on your steady state curve), but practically speaking, 12 hours post-dose is often the standard. The important thing is to be consistent. If I normally get my lithium level drawn 10 hours post-dose, but the next time I go to the lab, it’s 14 hours post-dose, my level will be lower on the second measurement. Everything else could be the same, but the level will be lower simply because I’ve checked it at a lower point on that curve.

Elimination

Different medications leave the body in different ways. Lithium, for example, doesn’t undergo any kind of metabolism (change in form); the kidneys excrete it as is. A lot of drugs undergo some kind of metabolism in the liver, and then, in their changed form, they leave the body through the urine, feces, or a few other elimination pathways.

The reference range that you’ll see given for a given medication’s half-life can be huge, because the way a drug moves around in, and out of, my body isn’t going to be exactly the same as what it does in your body. That’s because our body compositions are different, my liver and kidneys aren’t necessarily doing their thing at the same time as yours, and a whole host of other factors.

Interactions

Drug interactions can also play a role. If I’m taking the antipsychotic clozapine and my doctor wants it hanging around in my body longer, they might start me on the SSRI fluvoxamine. What does that have to do with anything? Fluvoxamine inhibits (slows down) the type of liver enzyme that metabolizes the clozapine, which extends the clozapine’s half-life.

Several antiepileptic drugs that are also used as mood stabilizers (i.e. valproate, carbamazepine, and lamotrigine) affect each other’s metabolism, meaning they’re getting broken down faster or slower than usual, which doctors have to keep in mind when making dose changes.

And have you ever been told not to drink grapefruit juice with a medication? That has nothing to do with what happens in the stomach; it’s because grapefruit juice inhibits a particular type of liver enzyme. If that enzyme metabolizes your drug, that’s a problem, as it prolongs the half-life and more drug than expected is hanging around in your body.

Long half-life drugs

Drugs with a long half-life will be dosed less often than drugs with a short half-life. Those long half-life drugs can also take quite a while to clear out of your body entirely. This has implications for addiction and withdrawal. Methadone, which is an opioid that’s used for pain and for opioid substitution in addictions, has a long half-life. The upside is that keeps a pretty steady amount of the drug in the system. The downside of the long half-life is that getting off of it completely is a slooooow and unpleasant process. When someone is being tapered off of long-term benzodiazepines, switching to a long half-life benzo like diazepam makes it easier to do a smooth and controlled dose taper, but then the last part is slow and hard.

A long half-life can also be relevant when switching from one medication to another. If I was going to be switching from the SSRI fluoxetine (Prozac) to an MAOI antidepressant, I would need to have a 5-week washout between when I stop the fluoxetine and start the MAOI to give enough time for my body to fully clear out the fluoxetine.

Should you care?

I have no idea if any of this made sense. I’ve left out all the tedious area under the curve stuff (AUC this, AUC that, who the hell cares…) that made my eyes glaze over in pharmacy school 20 years (half a lifetime!) ago.

It shouldn’t be your problem to care about this kind of stuff; that’s what health professionals are there for. But I think it’s nice to know that there is a rhyme and a reason to things, even if you don’t know, or care to know, any of the specifics. It’s also fun for me to babble about obscure stuff that’s stored in my brain.

book cover: Psych Meds Made Simple by Ashley L. Peterson

Want to know more about psych meds and how they work? Psych Meds Made Simple is everything you didn’t realize you wanted to know about medications.

It’s available on Amazon and Google Play.

Ashley L. Peterson

BScPharm BSN MPN

Ashley is a former mental health nurse and pharmacist and the author of four books.

16 thoughts on “Medication Half-Life: What it Means and Why it Matters”

  1. Aww thanks for the shout out 😀 how does half life have to do with a drug not working any longer in your system i was on abilify for years and then boom it just wasn’t as effective… is there a correlation? Thanks as always for info.

          1. Hahaha, really. “Wash out” is another term. Can’t remember the clinical term hahaha.

            Also interested in the role of Inflammation when it comes to depression. Read some paper on how perhaps anti Inflammatory medication can help with depression, especially psychomotor retardation.

            1. Washout actually is a clinical term, but with a different meaning (waiting for one drug to clear out of your system before starting a new one).

              The inflammation-depression connection is an interesting one. A major barrier at this point is the drugs that have shown a benefit in depression are injectable monoclonal antibodies and are really expensive. At one point I tried prednisone as an experiment to see if that would have an impact, but I had a lot of side effects so didn’t stay on it long enough for it to be a useful experiment.

            2. Oh, good to know about “wash out” 😀

              Dang, injectable anti-bodies definitely cost. Immunoglobulin therapy is really really expensive already.

  2. You’ve described this, as you always do, so clearly and concisely. The graph went way over my head but everything you wrote made sense.

    I can’t say that I really think about med half life much other than whether something might not digest well because I don’t want it going through whole and getting stuck in the damn stoma (which has happened before) 😆 Good point on long half life with addiction and weaning off whatever it is then becoming a much more drawn out process.

    I think the more patients can learn about their bodies and their medications the better. You never know when it might come in handy.

    Angela’s question in the comments is a good one. Sometimes meds do lose effectiveness or appear to stop working after a period of use when your body gets so used to them. I find similar with shampoo – if I keep using the same one, even though it started out great, it eventually starts making my hair crapper than usual. Not sure how it relates to half life so I’d be curious on that one too.

    xx

      1. Maybe give it a try using a different one. Maybe it’s just me and my weird hair, but I find using the same one eventually loses effectiveness and makes my hair worse. I now mix and match.

        I read somewhere about the benefits of shampooing your hair twice; the first time is to get the build-up of old shampoo out of your hair, and the second is to work its magic. I’m too lazy for that and too sceptical because I thought it was to make us buy twice as much shampoo.

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