Highlighting pharmacokinetics, pharmacodynamics and mechanism of action

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US brand name: Brintellix
Generic name: vortioxetine

Pharmacology

Brintellix’s Half-Life & How Long Until It Clears Your System

Half-life: 66 hours. Plasma Clearance: About two weeks.

Steady State

Steady state is reached in 14 days.

Half-life is the average time it takes for you to process half of the drug’s active ingredient. If a drug has a half-life of around 24 hours and you take a dose of 100mg, you’ll have roughly the equivalent a 50mg dose after one day, a 25mg dose after two days, and so on. The rule of thumb is: multiply the half-life by five and you get how long it is for the dose you took to be cleared from your bloodstream1.

Steady state is the flipside of half-life. This is when you can expect to get over side effects caused by fluctuating amounts of a medication in your bloodstream. Often, but not always the same amount of time as the plasma clearance above.



How vortioxetine Works

the current best guess at any rate

Briefly Brintellix is like an oddball second-generation, or “atypical” antipsychotic that doesn’t affect dopamine combined with either an SSRI or an SNRI that has 70 times more effect on serotonin than norepinephrine2. So, based upon our Communications Interference Hypothesis of psychiatric and neurological conditions (or brain cooties as we often call them):

  • Brintellix treats depression by effectively raising serotonin levels in your brain.
  • It does so by letting your synapses soak in those brain juices for longer than usual by slowing (inhibiting) the mechanism of serotonin transmission deeper into the neurons (reuptake).
    • At 20 mg a day it might do the same for norepinephrine to enough of an extent to make a difference.
      • At least that’s how I read the pharmacodynamics data.
  • Depending on where, and to what extent that effect occurs, your brain is happier.
    • Unlike most meds, Lundbeck & Takeda have done a lot of work identifying where that happens.3
    • A lot of Brintellix’s serotonergic action happens in your hippocampus, prefrontal cortex, and the dorsal and medial raphe nuclei.
  • In addition to boring reuptake inhibition, Brintellix is also a 5HT1A agonist (Like BuSpar and Viibryd) and a 5HT1B partial agonist.
    • In English Brintellix enhances serotonin reception where it makes you happy and moderates reception where it … uh ….
      • 5HT1B, while less of a mystery than many of the others, still isn’t well-understood. Right now it’s known to suppress pain and affect the action of serotonin at other locations.
      • The triptan class of migraine abortives are all 5HT1B & 5HT1D agonists.
  • Brintellix is also an antagonist, in that it inhibits some of the serotonin your brain gets, at several receptors just like many second-generation antipsychotics (SGAs) do. The receptors Brintellix blocks are just different from most SGAs.
    • It blocks 5HT1D, which is the conjoined twin of 5HT1B. Geodon is the only other med I’m aware of that is a 5HT1D antagonist, and Stahl thinks that has something to do with why Geodon is the AP least likely to cause weight gain and mess with your blood sugar.
      • Does that mean Brintellix won’t cause weight gain? Only time will tell.
      • That may mean Brintellix doesn’t have much of a future as a pain med.
    • It blocks 5HT3, which Remeron does. 5HT3 antagonists are used to prevent puking (anti-emetics), so Brintellix keeps the GI problems most people have the first few days/weeks/months/years when they take an SSRI (or any other medication) from being worse than they could be.
      • No, really. If it weren’t a 5HT3 you’d probably never be able to keep it down. All the serotonin receptors in your gut would be going batshit.
    • 5HT3 may also affect how cells transmit serotonin.
    • And it blocks 5HT7, which is linked to your sleep cycle and circadian rhythm, and thus indirectly to depression. Too much or too little serotonin here can cause problems, so it’s a coin-toss as to this being a good or bad thing when it comes to effects and side effects. Assuming it has any affect upon how you sleep in the first place.
      • Given the utter lack of insomnia or somnolence (too much sleep, daytime tiredness, etc.) side effects reported in the clinical trials, regulating your sleep cycle might be part of the reasons why Brintellix works.

Vortioxetine Pharmacokinetics

Since they did more work than most drug companies, I’d feel remiss if I didn’t include all the PK data.

  • vortioxetine is extensively metabolized by CYP2D6, CYP2C9, CYP3A4/5, CYP2C19, CYP2A6, CYP2C8 and CYP2B6
    • That’s more than amitriptyline!
    • From the PI sheet: poor metabolizers of CYP2D6 have approximately twice the vortioxetine plasma concentration of extensive [normal] metabolizers
  • PK is linear and dosage-dependent
  • Cmax values were 9, 18, and 33 ng/mL following doses of 5, 10, and 20 mg/day.
  • Tmax is 7 to 11 hours
  • AUC is 244 ng·h/mL
  • Apparent volume of distribution is 2600 L
  • Absolute bioavailability is 75%
  • Plasma protein binding is 98%
    • This, combined with being super-serotonergic in several different ways, is why you have to be extra careful when mixing vortioxetine and warfarin, NSAIDs, or anything else than deals with plasma.

The PI sheet says no dosage adjustment is required for any ethnic group, but with the data being mixed on the extent to which CYP2C9 is involved, and the reports I’ve read involving Zoloft, a weak-to-moderate inhibitor of CYP2D6, CYP2C9 and CYP3A4/5, my money is on a lot of Asians maxing out at 15 mg a day, if not 10 mg.

Active Ingredient

vortioxetine hydrobromide

The active ingredient is usually the same as the generic name, but more often than not it’s a chemical salt of the substance identified as the generic. E.g. Fluoxetine is the generic for Prozac, but the active ingredient is fluoxetine hydrochloride (or HCl). It usually doesn’t make much of a difference outside of the more esoteric aspects of a drug’s pharmacology, but not always.



Shelf Life

30 months in a bottle, 4 years in a blister pack



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1 After five times the half-life you'll have reached what's called "Plasma clearance," or "not enough left in your bloodstream to latch onto your brain and do anything." It's based on Julien's calculations from A Primer of Drug Action, and half-life multiplied by five is the generally accepted estimate of how long it takes a single dose of any given drug to be eliminated from the blood stream/plasma of someone with a normal metabolism. That's also the rough estimate for steady state if they can't get, or won't provide a number for that.
The next level is "Complete clearance", and is a complex equation based on a lot of factors which may or may not: be published in the PI sheet, include personal data like your weight, or even completely figured out by corporate and independent researchers. It usually winds up being within (as in usually, but not always, after) 2-5 days of plasma clearance no matter what, but sometimes can take weeks. Sometimes a drug will clear from your brain and other organs before it clears from your blood.
That's how it works for crazy meds. I have no idea what the average complete clearance is for other types of medications. For all I know there are drugs that utterly vanish from your system in under five passes, and others that won't let go of your squishy bits for years after you stop taking them.

2 Hence it is one of the few ADs to which the term "atypical antidepressant" truly applies.

3 As far as serotonin is concerned. Everyone is ignoring norepinephrine.


Last modified on Wed, 04 May, 2016 at 16:42:05 by JerodPoorePage Author Date created Thursday, 02 October 2014 at 15:17:50
“Brintellix (vortioxetine) Pharmacology” by Jerod Poore is copyright © 2014 Jerod Poore Published online 2014/10/02

Brintellix, and all other drug names on this page and used throughout the site, are the trademarks of someone else. Brintellix’s PI Sheet will probably have the name of the manufacturer and trademark owner (they’re not always the same company) at or near the very bottom. Or ask Google who the owner is. The way pharmaceutical companies buy each other and swap products like Monopoly™ real estate, the ownership of the trademark may have changed without my noticing. It may of changed hands by the time you finished reading this article.



Page design and explanatory material by Jerod Poore, copyright © 2003 - 2016. All rights reserved. See the full copyright notice for full copyright details.
Don’t automatically believe everything you read on teh Intergoogles. No warranty is expressed or implied in this information. Consult one or more doctors and/or pharmacists before taking, or changing how you take any neurological and/or psychiatric medication. Your mileage may vary. What happened to us won’t necessarily happen to you. For more details see the Crazymeds big-ass disclaimer.

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