Highlighting pharmacokinetics, pharmacodynamics and mechanism of action


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US brand name: Effexor
Generic name: venlafaxine


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

The half-life of venlafaxine is 3–7 hours, and o-desmethylvenlafaxine’s is 9–13 hours. That means it takes two days for one and five days for the other to clear out of your system.

Steady State

three 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 venlafaxine Works

the current best guess at any rate

Venlafaxine Pharmacodynamics

Based upon the monoamine hypothesis of depression (i.e. you’re messed up due to an imbalance of one or more of three of the best understood neurotransmitters: serotonin, norepinephrine, and/or dopamine), Effexor attempts to balance your brain juices by inhibiting the reuptake (in English: delaying the breaking down and recycling) of serotonin and norepinephrine at their receptors in various (i.e. depending on which studies and books you’ve read and fancy brain scans you’ve looked at) locations in your brain. It may do a lot of other things that address depression, anxiety, other brain cooties and some off-label uses by encouraging the growth of new neurons, affecting hormones and CYP450 genes in your brain, and who knows what else. You also have serotonin and norepinephrine receptors throughout your body, especially in your GI and renal systems, which is why SSRIs & SNRIs are used to treat various conditions like IBS and incontinence. As it doesn’t really affect norepinephrine until you reach a dosage of at least 225mg a day (or 175–200 for IR), it is practically an SSRI, and thus not as effective for pain and pain-related conditions like fibromyalgia as other SNRIs like Cymbalta and Pristiq.

The active metabolite o-desmethylvenlafaxine (ODV) does most of the work, and is now available in a refined form as Pristiq ( desvenlafaxine ).

Venlafaxine Pharmacokinetics

When you compare venlafaxine with other SSRIs and SNRIs you’ll find, in terms of raw potency, it’s the weakest reuptake inhibitor of any med defined as a serotonin- or norepinephrine-reuptake inhibitor. So why is it so effective? And, presumably, why are its discontinuation symptoms so awful? The answer has to be found in its pharmacokinetics (PK).

The half-life of venlafaxine HCl is 3–7 hours , and ODV’s half-life is 9–13 hours . That means it takes two days for one and five days for the other to clear out of your system. Having two parts with short half-lives is a huge part of why the discontinuation syndrome is so freaking harsh.

The other PK stats for venlafaxine XR and ODV are:

  • PK is linear
  • Cmax 150 ng/mL for venlafaxine and 260 ng/mL for ODV
  • Tmax is 5.5 hours for venlafaxine and 9 hours for ODV
  • Apparent volume of distribution is 7.5±3.7 L/kg for venlafaxine and 5.7±1.8 L/kg for ODV
  • Steady-state plasma clearance is 1.3±0.6 L/h/kg for venlafaxine and 0.4±0.2 L/h/kg for ODV
  • Absolute bioavailability for venlafaxine is 45%
  • Plasma protein binding is 27% for venlafaxine and 30% for ODV
  • 92% of a single oral dose of venlafaxine is absorbed.

That last parameter is something I rarely see anywhere. When I do see it, it’s never close to 50%. While venlafaxine’s absolute bioavailability is low, the low plasma protein binding, spectacular, as far as I can tell, absorption, and truly spectacular Cmax (Twice as high as the similarly weak bupropion and 4–5 times greater than all the other antidepressants where I have that number) explains why a drug with such a piss-poor effect on the neurotransmitter transporters is so freaking effective. Basically what it lacks in strength it makes up for by getting more of the active ingredient where it needs to be.

So if this site ever starts making money again I’ll have to get the numbers for a lot of other meds and do the math to update the equivalencies.

Active Ingredient

venlafaxine hydrochloride and the active metabolite o-desmethylvenlafaxine

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

3 years

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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.

Last modified on Wed, 04 May, 2016 at 17:11:29 by JerodPoorePage Author Date created Monday, 25 April, 2011 at 11:53:36
“Effexor (venlafaxine) Pharmacology” by Jerod Poore is copyright © 2011 Jerod Poore Published online 2011/04/25

Effexor, and all other drug names on this page and used throughout the site, are the trademarks of someone else. Effexor’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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