Buprenorphine

QuestionsCategory: OpioidsBuprenorphine
Sergey asked 2 weeks ago

I don’t understand something so basic that it’s been driving me crazy for years and now I’m on a mission to solve that (by , I hope, asking this question:)):
Buprenorphine+naloxone combos for OAD, contain an agonist and an antagonist, to put it short. How is it feasible? I mean, try giving someone pretty much any mu agonist together with naloxone and, in as long as the doses are proportional, the antagonist prevails since it has stronger binding activity, right? That’s the basic principle behind opioid overdose reversal, no? There’s of course the argument that Buprenorphine’s binding to receptors strength is higher then that of Naloxone’s… Ok, let’s consider it for a sec: these two don’t absorb at the same rate, coz one is, respectively, short-acting while the other is long-acting. So if taken together (thru mucous surfaces), Naloxone would absorb pretty much in a very short period of time, but not so for Buprenorphine… So how is it then, when an individual takes a Suboxone pill, he is not instantly in precipitated withdrawal due to Naloxone presence? I always thought that the latter would ONLY be absorbed by the body if the combo is misused thru IV, otherwise there’s a big piece of the puzzle I am missing. Please explain. Thanks

1 Answers
Jeffrey Fudin Staff answered 2 weeks ago

Sergey,  The answer to your question is simple. Naloxone SL is not absorbed as well at buprenorphine, and the dose is very low compared to buprenorphine, which as you acknowledged, has a higher binding affinity.The intent of adding naloxone originally was to discourage people from making an IV formulation out of the SL product, and injecting it.  I do agree with you though – the combo is nonsense for various reasons related to the lipophilicity of each drug and their partition coefficient which is a value that determines how quickly a drug passes through the blood brain barrier.  To learn more, see Gudin J, Fudin J. A narrative pharmacological review of buprenorphine: a unique opioid for the treatment of chronic pain. Pain and therapy. 2020 Jun;9(1):41-54. IOt is at https://link.springer.com/article/10.1007/s40122-019-00143-6.