Mucosa

Optimizing Absorption of Buprenorphine

A ‘quick one’…  I have written before about getting the most buprenorphine from a God-awfully expensive tablet of Suboxone, and will repeat myself for newcomers.  Note that my description is based on an understanding of pharmacology, organic chemistry, and physiology– NOT on the recommendations of Reckitt-Benckiser or the FDA.  My suggestions also come from knowledge of other, similar medications that are absorbed through mucous membranes– for example fentanyl, which is dispensed with a trans-mucosal delivery system for cancer pain.

A bit of background…  the reason you can’t just swallow a tablet of buprenorphine and expect it to work is because of something called ‘first pass metabolism.’  The liver is very good at breaking down buprenorphine in MOST people.  Buprenorphine and other medications, if swallowed, pass through the lining of the small intestine into the ‘portal vein’, which delivers them very efficiently to the liver, where they are effectively metabolized.  Some medications including fluoxetine (Prozac) will interfere with liver metabolism; I have not seen studies showing the levels of buprenorphine in such cases, but I would presume that levels of buprenorphine would be higher in general in people taking fluoxetine, especially comparing levels in people who swallow buprenorphine tablets whole.  As an aside, naloxone, the other ingredient in Suboxone, is also rapidly destroyed by ‘first pass metabolism.’  Because of first pass metabolism, little naloxone or buprenorphine accumulates in the bloodstream after oral ingestion.

Buprenorphine diffusion
Schematic of Oral Mucosa

Suboxone is therefore designed to be taken ‘trans-mucosally’, i.e. via absorption through the lining of the oral cavity into the bloodstream (the lining of the oral cavity is called ‘mucosa.’  The passage of molecules through the oral mucosa is affected by a number of things– the size of the molecule, the lipid solubility of the molecule, the concentration of the molecule, etc.  Buprenorphine is a lipid-soluble molecule that passes through the mucosa relatively easily, whereas naloxone is more water-soluble, and crosses the mucosa very poorly.  THAT is the basis for why the naloxone in Suboxone is not active;  only buprenorphine enters the bloodstream in significant amounts through the oral mucosa, and BOTH buprenorphine and naloxone are destroyed after being swallowed.

The goal with buprenorphine is to keep a level of the medication in the bloodstream that is above the ‘ceiling’ level– the level where the maximum opiate effect is obtained, above which no more effect can be gained with higher levels.  If the blood level stays above that ceiling level during the entire interval between doses, there will be no drop-off in opiate effect, i.e. no withdrawal, and no cravings for opiates (except for psychological cravings that can be quite intense initially, but that can be reduced through proper use of the medication.)  A constant level above the ‘ceiling’ is also necessary to prevent feeling ups and downs while on the medication.  If the level remains above the ceiling point, the person feels ‘normal’ all of the time, and gets no ‘high’ from taking the medication.

Suboxone is, of course, too expensive;  the generic form of Subutex was initially priced at about $2.50 per 8 mg tablet, but the price is now approaching the price of brand-name Suboxone.  Some people require higher doses of medication than others, depending on body size, liver function, other medications, and other factors.  Most of my patients take around 12 mg of buprenorphine per day;  some take 8, some take 16, and some take doses as low as 2 mg per day.  In my experience the need for doses above 16 mg is rare, and if a person is getting ‘withdrawal’ at 16 mg I consider ineffective dosing as a potential problem.  In some cases the ‘withdrawal’ is actually psychologically-based, and would not respond to any dose of buprenorphine without an intervention to correct the patient’s perceptions.   But when the problem is ineffective dosing, I have seen very good results by making some changes in the way the person takes the buprenorphine, in order to optimize absorption.  Here was my suggestion to optimize absorption for a person who wrote to me the other day:

Absorption of buprenorphine is affected by a number of factors.  The three things that affect absorption that you can control are the concentration of buprenorphine in solution, the amount of surface area for buprenorphine to pass through, and the time allowed for absorption to occur.  So start with a dry mouth (swallow first), then crush an entire tab between your teeth to get it dissolved right away, in a very small amount of saliva.  That will increase the concentration of buprenorphine in solution, driving the diffusion of the molecule down the concentration gradient, into tissue.  Then ‘paint’ all of the surfaces in your mouth using your tongue as the paintbrush.  Try to spread the concentrated mixture over every surface;  there is nothing special about the tissue under the tongue.  The buprenorphine molecule will stick to the fresh surfaces, then pass through the mucosa, eventually diffusing into the bloodstream at a capillary.  After painting and re-painting the oral surfaces for 10-15 minutes, you can swallow the rest;  most of the absorption will have occurred by that time.   Be sure not to eat or drink for at least 10 minutes, though, so that buprenorphine molecules that are bound to the mucosa are not rinsed away, and rather can be absorbed.

I have seen good responses to this technique.  I have also been told that taking buprenorphine in this way shortens the time that it takes to dose.  For those who hate the taste, try putting an Altoid or half of a Life Saver in your mouth while dosing;  just avoid increasing the volume to a large extent, as that will reduce diffusion and absorption of buprenorphine.  You could also try sucking on an ice cube and then dosing, as the cold will reduce the function of your taste buds;  I would have a little concern, though, that absorption of buprenorphine will be slowed down by the cold as well, since blood flow through capillaries will be reduced after chilling the mucosa.

I expect there eventually to be a number of options for taking buprenorphine.  Hopefully we will eventually have some ‘American-style competition’ that gets the price per tablet out of the stratosphere!

5 thoughts on “Optimizing Absorption of Buprenorphine”

  1. So, I have been trying this method out for the last 3 days, and here is the thing,
    I have to believe it’s working great, I recently started sub at 16, and now with your method am at 8 and feeling great. However, I have a HUGE amount of saliva that builds in my mouth as soon as I crush the tablet with my teeth. I still try to ‘paint’ the inside of my mouth with the extremely diluted solution for about 10 minutes, and then after a bit, I just swallow.
    So, is this normal? As I said, I am still feeling fine with 8 per day, but it dont get that concentrated solution that you talk about in your article.

    Thanks.

  2. Actually, all surfaces of the mouth are not created equal. The bio-availability of buccal ( through the cheek) absorption of buprenorphine is around 30%, compared to about 50% sub-lingual ( under tongue). This is due to the relative thin skin and absence of mucous, as well as the presence of several large blood vessels,on the lower surface of the tongue. The manufacturers patient handouts for administration of suboxone (film) contains diagrams showing correct placement on lower surface of tongue ( on top of the visible veins that reside there).

  3. Sorry to disagree. The large blood vessels– proper term ‘venules’– are surrounded by multiple layers of connective tissue, and play no significant role in absorption– just as they play no role in exchange of oxygen or carbon dioxide. The veins are like superhighways, without any on or offramps– and the exchange of molecules occurs at street level! Even the capillary beds are less accessible under the tongue; the sublingual salivary glands empty there, causing a constant current that channels beside the tongue and down the throat, out of most peoples’ awareness.
    The little picture by the manufacturer is intended for the same people who need warning labels on cigarette packages.

  4. So, you are saying that the capillary beds themselves,” street level”, are actually less accessible sublingually than some of the other oral surfaces. I feel like one of those guys who needs to read the directions on a shampoo bottle, and never finishes (wash, rinse,repeat…). I guess I shouldn’t try to argue medicine with a doctor! The films “fit” so well under the tongue, however, I will probably just continue sticking them there for convenience sake, instead of where I WAS putting them(I’d rather not say) before I saw the R-B cartoon. Great site (best of it’s kind) ,and thank you for setting it up, it seems to help a lot of people.

  5. In the USA They can now prescribe Bup in a 2 or 8 MG tab. (It’s also now being used a lot by vets Dr’s on domestic pets because you can’t OD your pet. It’s basically because fido the dog can’t tell you when he’s had too much.)

    The main problem in getting the best absorption is that your mouth fills with saliva and dilutes the compound in your mouth causing you to prematurely swallow it making it inert. If you get you Bup or Suboxone in a form that can be ground up (not films) try this. Get some powered “instant food thickener” (Hormel Thick & Easy is a brand widely available in the USA). This is a white powder that looks like very course sugar or salt. Mix in about 150% of the thickener in volume compared to the ground up medication and mix them throughout. Using a small bowl and a spoon works just fine to grind the two together into a fine powder. Now when you put this powdered mix under your tong it will turn to a gel like consistency, making it easy to keep there for considerable time. This really works!

    Unfortunately most of the other ideas I have read here are questionable at best as they sound good, but don’t work in the real world as you end up swallowing it during the “paint” job. I’ve seen results with this food thickener method where the powdered jel is still in place under the tong after an hour or more; even if the subject took a drink of water or soda. Often you have to move the jel around a bit to get it to dissolve fully. Move it just slightly by grinding it around under your tong.

    Many people are paying $8+ a day for an 8MG tab, this method may allow you to use only 4 MG and stretch out a 30 day supply to a 60 day supply. If you doing H and using Bup (Suboxone) to make it to you next fix STOP IT! Your life is a mess, you have lost control of it. Just go to a doctor and switch over to Bup or Suboxone full time instead. Your life will be all new in 30 days or less, guaranteed! Then you can slowly ween off it, or keep on taking it (Bup) Either way you will then have the opportunity to get control of your life again for only a few dollars a day even if you don’t have insurance. Praise God!

    P.S. I’m not a doctor, use at your own risk, don’t blame it on me, blah blah blah blah blah. :-)

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