Optimizing Absorption of Buprenorphine

I wrote this a couple years ago, and still get questions about the topic today.  Studies show that a small fraction of the amount of buprenorphine in a tablet or film strip actually gets absorbed through mucous membranes;  the rest is swallowed.  The 15%-30% amount of absorption is referred to as the ‘bio-availability’  of the drug.
People who feel like they are not getting enough buprenorphine to remove cravings can review the principles below, to see if there are ways they can easily improve the absorption of buprenorphine.  NOTE:  improving absorption is NOT an ‘addictive’ behavior, for a couple reasons…. first, because of the ceiling effect, increasing the amount absorbed will NOT cause a ‘buzz’ or high, but will only make the medication last the full 24 hours without wearing off.  Second, crushing a tablet will NOT cause a ‘rush’ or ‘high’ for two reasons– first, because of the ceiling effect as I just described, and second, because the rate-limiting step for absorption is the passage through tissue— NOT the dissolution of the tablet.  This is why, by the way, the film does not cause a ‘rush’, even though it dissolves more quickly.
Read on:
I often answer questions about Suboxone that require the qualification ‘if it is being absorbed properly’. If a person asks how long it takes for Suboxone to wear off, or at what dose does the ceiling effect occur, I need to be sure that the person is taking it in a way that maximizes absorption; otherwise all bets are off. If a person simply swallows the tablet, for example, the level of buprenorphine in the bloodstream will be much lower than if it is taken correctly.
The usual instructions for taking Suboxone are to place a tablet under the tongue and let it dissolve.  It is important that Suboxone be taken once per day, in the morning; this instruction is included in the course for physicians but is too often ignored.  I will talk another time about the philosophy for dosing once per day; the basic reason is to extinguish the behavior that has been conditioned as part of the addiction.  But the point of this post is the absorption of buprenorphine from the tablet into the bloodstream, and how to maximize that absorption.  It is important to maximize absorption, particularly if one is trying to save money by reducing the daily dose of Suboxone.
From my experiences as an anesthesiologist, as an addict**, and as a PhD chemist, I recognize that three factors will maximize absorption.  The first is the concentration of buprenorphine in the saliva, as the drug diffuses into tissue down a concentration gradient.  This gradient is maximized by having a small volume of saliva.  I recommend that a person start with a dry mouth, place the tablet in the mouth, and crush the tablet between the teeth until it is dissolved in a small volume of a concentrated solution.
The second factor that affects absorption is the amount of surface area.  Buprenorphine is absorbed through all mucous membranes (the tissue lining the inside of the mouth), passing through the surfaces and entering capillaries, the route into the bloodstream.  So the concentrated solution should be ‘painted’ repeatedly over all of the surfaces inside the oral cavity;  the inside surface of the cheeks, the tongue, the roof of the mouth, under the tongue, the back of the throat…  swished around in the mouth over and over, repeatedly bringing the concentrate into contact with new areas of mucous membranes.
The third factor is time– the longer period of time, the longer for the buprenorphine to make contact with the mucous membranes, attach to the surface, get absorbed into the tissue, and enter the capillaries.  The initial process will be the saturation of the surfaces of the mucous membranes, and the slower process will be the passage into the tissue;  that is why the amount of surface area has such an important effect on absorption.  Fifteen minutes is probablysufficient for most of the absorption to occur;  there may be drug remaining that is attached to the surface but not yet fully absorbed, and so I recommend avoiding eating or drinking within another fifteen minutes or so after swallowing the left-over saliva.
If you pay attention to these principles you will maximize absorption of the drug.  The ceiling effect will occur under these conditions at a dose of about 2-4 mg;  the long half-life of the drug will guarantee that if you take over 4 mg or so each morning, you won’t have any significant withdrawal for over 24 hours– allowing once-per-day dosing.  Yes, early in treatment patients will feel as if they need to dose more frequently– but that is not because of too little buprenorphine, but rather because of conditioned behavior.  A person early in Suboxone treatment will have feelings or minor withdrawal in the late afternoon or evening after dosing in the morning;  those minor withdrawal sensations will go away in about 15 minutes if the person takes more Suboxone, and will also go away in 15 minutes if the person doesn’t take Suboxone.  If the person takes more Suboxone, it will reinforce the sensations and the person will get stuck on dosing twice per day.  If, on the other hand, the person uses distraction and avoids dosing, those minor withdrawal sensations will completely disappear in a week or two, as the conditioned behavior is extinguished.
**I mentioned my experience ‘as an addict’;  for a period of time my preferred route of administration of lipid-soluble opioids was ‘trans-mucosal’ or ‘trans-buccal’.  Since the amount of substance available was finite (albeit a fairly large finite amount!) I did all that I could to optimize absorption, including reading about diffusion of lipid-soluble molecules through mucous membranes.

Generic Subutex, aka buprenorphine– what's the dif?

I’ll take a break from the book to post a question and answer with a reader:
My daughter’s doctor recently started prescribing her a pill called only ‘buprenorphine,’ instead of her usual Suboxone. Should I be concerned about the change?
My answer:
You don’t mention the age of your daughter, but your question raises the issue of how involved should a parent be in the treatment of a child?  Perhaps a more general issue is whether anyone should be closely involved in the treatment of someone with opioid dependence?  After all, I frequently write that opioid addiction should be seen as ‘just another disease,’ and it is hard to make the case that people should share the details of their medical histories with others, at least after reaching adulthood.
But opioid dependence, while being a disease, does have some unique qualities—such as the effect of a worsening of the disease, i.e. relapse, on patients’ ability to make sound judgments.  Over time, I typically want patients to become responsible for their own outcomes; adult children of too-involved parents sometimes seem to be stuck in a state of chronic defiance, where the addict seems to think that a relapse is a statement of independence or a reflection on the parents, rather than the addict’s own problem.  But early on, it can be helpful to have someone monitor the addict’s behavior, and even control the buprenorphine.  Just remember that only the addict him/herself can determine, in the long run, whether a buprenorphine program will work—or whether it will just be one more failed treatment method.
Suboxone and Subutex (generic or brand-name) are interchangeable for the most part— except generic buprenorphine is about half the price of brand-name Suboxone  ($3 per tab vs. $6-$7).  The main chemical difference is the naloxone in Suboxone, which is not present in Subutex or generic Subutex (aka buprenorphine HCL).  Naloxone doesn’t cross mucous membranes; lipid soluble molecules like buprenorphine and fentanyl tend to pass through mucous membranes, and water soluble molecules like naloxone and morphine do not.  When a person takes Suboxone properly the naloxone ends up being swallowed, absorbed from the intestine into the ‘portal vein,’ and then completely metabolized at the liver before getting into the systemic circulation by a process called ‘first pass metabolism.’  The features of buprenorphine that make it effective for treating opioid dependence (for example the ‘ceiling effect’) do NOT require naloxone. Naloxone is added to Suboxone for one reason—to prevent intravenous injection of dissolved Suboxone tablets.  If Suboxone is dissolved and injected, the naloxone would enter the circulation, block opioid receptors, and cause an hour or two of withdrawal symptoms. 
There is not a great amount of injecting of Suboxone going on out there, and so for most people, generic buprenorphine is fine.  Some people who don’t completely metabolize the naloxone (because of genetic variants of liver enzymes, or perhaps because of taking cytochrome inhibitors like certain SSRIs) develop dysphoria for an hour or two after a dose of Suboxone, because the naloxone gets into their systemic circulation and causes withdrawal.
All patients who are pregnant are generally put on Subutex (or generic buprenorphine) because the low chance of injecting is not enough reason to expose the fetus to one more chemical.
I don’t know if your daughter is pregnant, but that would be one reason to take the generic.  Or it may be a cost issue, or perhaps she sometimes felt sick after taking her dose of Suboxone.  The theoretical risk from switching would be that she could then inject the buprenorphine, without the risk of withdrawal.  If she DID inject, she would not get ‘high’ from doing so;  the injected buprenorphine would have the same effects as when it is absorbed through the oral mucosa, only more quickly (i.e. zero effects, more quickly!).  Even for people NOT tolerant to buprenorphine, injecting buprenorphine is not generally a great way to get high;  the person develops a tolerance to buprenorphine very quickly, and within a day or two is ‘on’ buprenorphine going forward–  incapable of feeling opioid effects because of mu receptor tolerance, and vulnerable to withdrawal if the buprenorphine is discontinued.
I’ll be back with another installment of the book in a few days.  Thanks, as always, for reading; please share the site with other addicts and with those who love them.
JJ