Two important questions about Bupe. (suboxone)

[teddybearpicnics]

This is a question about any form of bupenorphine that swim has been wondering about for quite some time...

If an individual is on suboxone, say 8 mg's a day, for a month..no slips ups, and then stops using it, will his opiate tolerance be just as low as it would be if he went cold turkey?

Basically, since bupe is a partial agonist/partial antagonist, does that actually let your opiate tolerance go down, or are you still as tolerant because the receptors are still getting filled for the duration prescribed.

______

Swim was also wondering this...

Since the mean half life is 36 hours, does that mean that your receptors are filled for that long...or that it is just in your system, the fat cells, wherever it stores itself...I don't know. But really, in theory, If you are on 8 mg's a day, that means that in 24 hours you still have 6 mg's in your system, so then if you take another 8 mg's...you're up to 14, then the next day you still have like 11.xx mg's in your system...and so on. So the question is...In a couple days the patient would have such a high build-up of bupe it would seem that they'd hit the ceiling, but why then in a little over 24 hours is he feeling the sickness. Hope someone can answer these questions and I cannot find any answers elsewhere.

.teddy

[Richard_smoker]

i'll try to address your question to the best of my ability. unfortunately, the question is a little all-over-the-place.

you're correct in your assertion about the 'building up' of active levels of buprenorphine by taking it once/daily. what you're not taking into consideration is that most of that built-up bupe is actually on its way DOWN.

in other words, lets say there's 2mg lingering in your system from 2 days ago, and 5mg lingering from yesterday's dose. you're accustomed to taking an additional 8mg every day to top off the 7mg lingering around. This means that your 'usual' level after taking your daily dose is approximately 15mg traveling throughout your bloodstream.

But you must consider that the 2mg from 2 days ago is dropping off very quickly. By tomorrow, those 2mg will be essentially zero. And the 5mg from yesterday is rapidly decreasing as well--by this time tomorrow, you'll only have 2mg of it remaining in your system. The 8mg that you took today is the most potent, longest-lasting bupe in your system. Even by this time tomorrow, it will have only gone down to 5mg.

Essentially what you're experiencing when you feel "the sickness" is that your TOTAL current blood-levels of buprenorphine have fallen below your own arbitrary 'cut-off' level.

Not adding the fresh 8mg into your system every 24 hours will essentially leave you high and dry VERY QUICKLY.

here's our hypothetical example except SKIPPING an 8mg dose:
there's 2mg lingering in your system from 2 days ago, and 5mg lingering from yesterday's dose. On this day, you SKIP your 8mg daily dose, leaving you at only the the 7mg lingering around in your system. Now, remember from the other example that your 'usual' level after a daily 8mg tab is 15mg total. Well, right now you only have 7mg. after an additional 24 hours, that 7mg will drop down to around 2mg.

with a buprenorphine level that LOW, you begin to experience the "sickness" that you describe.

UNDERSTAND??? Let me know if i need to clarify better. These numbers are not exact. they're just demonstrating a point in pharmacodynamics that not many people understand.

This tendency of bupe to behave in this fashion is why it is best to taper your dose SLOWLY down to zero--if you're quitting. and it also explains why even the TINIEST doses (like 0.02mg) are effective at fighting off dope-sickness when tapering.
-DICK

Reputation Comments on this post:

	good explaintion for the op
	easy to follow and thorough explanation, thank you for posting :)

[teddybearpicnics]

Okay thanks for the reply...now swim has another question.

Does the half life system work like this...

8 mg dosage...36 hours later, swim has 4 mgs in his body.
36 hours later, is that 4 mg's cut in another half, or is it one steady rate, meaning that another 4 mg's would be out.

To swim, it makes sense that it would be going constantly steady, not always dividing in twos, our bodies don't work by numbers. How would it always be on a timeclock dividing in twos. But, on SOF, there was an explination that it was saying the opposite of what swim thinks. So, if that could be cleared up swim thinks it would help a lot of poeple understand better.

Swim understands your post completely, other than the question he just added. But swim is not used to any certain amount in the blood stream, so as for the reason swim feels sick a day later, he doesn't understand because he can go on a week long bender, and then take 2mg's of suboxone, and it makes him feel 100% fine, but if he takes 8 mg's of suboxone, 24 hours later he would still have 4 mg's in his system but he is feeling sick. Maybe even though it is still in the plasma the binding isn't still there...correct?

And what about the tolerance question?

.teddy

[gmeziscool2354]

yes, every 36 hours 1/2 of the remaining material would be excreted

so 8 to 4 to 2 to 1 to .5 to .25 to .125 ect every 36 hours

[Richard_smoker]

yes, but don't take this literal definition to apply to all drugs and all situations like an equation you can just punch in numbers for. it depends on exactly what you're talking about--zero order kinetics, first-order kinetics, what the concentration of drug is in the body prior to the last dose, how long have you been on the drug, and some others...

but if you're talking about how much of EACH DOSE do you still have in your system (not talking about any of the doses before), then yes, every time a half-life passes by, your body will eliminate exactly HALF of the drug--resulting in exactly what gmeziscool2354^^^ said. 8mg--(36hrs later)-->4mg--(36hrs later)-->2mg etc etc

[Dickon]

I wrote about the mathematics of this at some length on "Screaming". It's an easy post to find, because it's long, and has rows of numbers in it. I am talking here about 1st order kinetics (i.e. things that have half-lives). I also posited a completely lay explanation for 0th order kinetics, which I'd love to hear Dick's view on.

Let's do a Kindergarten example, with 36 hour half lives. We'll work in days, so that's a half life of 1.5. So starting with a single dose of x mg (we ignore the actual time for absorption (small c.f. half-life so irelevent), and the bioavailability (effectively a constant multiplier in front of the equation, so irrelevant), and work out how the body-load (I'm sure there's a technical word for this which Dick will tell us) varies with time.

This is x.(0.5)^t/1.5 or x.(1/2)^2t/3.

As a^b.c = (a^b)^c we can write this as x.((1/2)^2/3)^t.

A quick zap with a calculator will tell us this is roughly x.(0.63)^t.

So, let's work out what the steady state solution is for a daily dose of x mg. In fact, let's pretend x is 1 for now, then we can simply work out what happens for 1 mg, and multiply by x when we're done. Maths is all about being lazy, and making things easy.

ok we'll have two columns for each day, initial body-load, and body load post-dosing with 1 mg.

Day 1 0 mg,1mg
Day 2 0.63mg,1.63mg (0.63*1 is 0.63. 1.63=0.63 plus the next dose of 1 mg)
Day 3 1.03mg, 2.03mg (1.03 is 0.63*1.63, 2.03=1.03+1 etc).
.
.
.

Notice 2.03=1 + 0.63 + 0.63² (I've rounded some numbers).
In fact, (I leave why as an exercise for the reader), after a large number of days the maximum dose will be D_max= 1 + 0.63 + 0.63² + 0.63³ + ... + 0.63ⁿ + ...., and the minimum dose will be D_min=0.63*D_max (also =D_max-1. Why?).

Now D_max = 1 / ( 1 - 0.63 ) [the formula for the sum of the terms in an infinite geometric progression] which equals 2.7 or there abouts.

OK now we're getting to the nitty-gritty. For daily dosing of a compound with a 36 hour half-life, the maximum body-load will be 2.7 times the daily dose, and the minimum daily dose will be 1.7 times the daily dose.

If you want to do this calculation for other substances with daily dosing and a half life of p days, work out q which equals (1/2)^1/p, and then D_max will be 1/(1-q), and D_min will be q/(1-q). Notice that the significance of q is that it is the proportion of stuff remaining after 1 day. To see that this makes sense think p=1/2, q (for this p)=(1/2)^1/(1/2)=1/2²=1/4, which is obviously right. If a drug has a half life of 12 hours, a quarter will remain after 24 hours. [Maths lesson, if you have a formula for something, check it with a "mickey mouse" example. It won't prove it's correct, but if you're wrong, it might help you pick it out. Sorry, I'm a mathematician sometimes!!]

So, just to go back to teddy's example of 8mg, we simply multiply 2.7 by 8 to get 21.6mg as maximum body load, and 13.6mg as minimum body load. If you wait 48 hours you will be down to 8.6mg and if you wait 72 you'll drop to 5.4mg (each of the numbers 21.6,13.6,8.7,5.4 is obtained by multiplying the preceding one by 0.63).

For those interested in methadone, which has a half-life of about 24 hours, these calculations are far easier as p=1 so q=1/2, D_max=2,D_min=1.

I don't know if this is a case of "this book teaches me more about turtles than I wanted to know", but it's useful to know these calculations exist and how to do them. It explains why and how drugs with long half-lives build up in the system, and how the body-load can be significantly higher than the daily dose.

I think the initial question was about cross-tolerance. If you took 8mg of buprenorphine a day for a time, and stopped substituting another opiate, what would be the equi-analgesic (equi-euphoric?) dose? I'm afraid I can't help with this one - sorry.

Keep smiling and learning

Dickon

[Richard_smoker]

wow. i got kinda stuck in the actual mathematics of what you were saying, but after skipping down, it makes sense.

not sure what you mean by body load unless you're referring to the actual concentration of drug that remains dissolved in the entire system (from previous doses).

one other little tidbit from pharmacology math-made-simple is that i believe it takes 5 complete half-lives for your body to establish a 'steady state' of drug levels to be maintained 24/7.

5 half lives of buprenorphine would be 7.5 days.

If my assumptions are correct, the MINIMUM time between tapers should be 7.5 days to allow your levels of buprenorphine to actual level off at your current (decreased) dose. Does this sound right? Dickon?

at any rate, it certainly "feels" about right. 7 or 8 days between step-downs is a must, lest you find yourself tumbling head-over-heels with heavy rigors and scary-looking "pill-rolling" tremors that look more like parkinson's disease than withdrawal.
-DICK

-DICK

[teddybearpicnics]

Wow I definitly got lost in those equations, I had to take that shit very slow, and I'm still confused about the body load factor. But nontheless, Dickon, you always amaze me with your intelligence and care to answer questions in the most professional way. So even though I am still kind of puzzled with the math, You made sense to me what is going on...without the numbers.

So. Question one has been answered to the fullest extent, at least to this brain. Now how about the tolerance question.

Would one need to successfully taper down off the suboxone, and then go cold turkey for his actual opiate tolerance to drop down to baseline? This worries swim because even though he wants to get off the smack, he loves opiates and would love if he could get a good buzz occasionaly from some percocets or an IR 30 oxy.

Thanks for all the help you guys are the best.

.teddy

[Richard_smoker]

tolerance would only drop back to baseline after being totally CLEAN off buprenorphine for at least a week.

if by "baseline" you mean BASELINE-BASELINE like pre-addict days, you're probably looking at several weeks, maybe a month or longer.

-DICK

[chillinwill]

You definitely would need to stop using Bupe in order for your tolerance to even have a chance to start returning back to "normal". Tolerance issues can still be displayed after a week but the longer you can go without using any opiate/opioid will help the tolerance issue lower

[teddybearpicnics]

So if you taper down from bupe to say 1 mg a day, and then go clean until it is all out of your system, your tolerance would still be sky high? That would make swim think that he would still be getting sick as fuck. Sorry if these questions seem stupid, they are just puzzling to swim.

[moda00]

Well, your tolerance is going down.. but yes you would still be getting sick because if you don't give your body that time to stabilize between decreases it throws it all off.. see above, lol I can't explain it right. I believe that is why you feel much less withdrawal the longer you leave between decreases- because you are giving your body time to get to a steady state and account for the change, and also allowing tolerance to decline. It's an interesting question though, now I am wondering about this lol.. RS, Dickon? If you dropped off from 1 mg after a taper to nothing, would your tolerance return to baseline-ish in the same amount of time as if you dropped off from say 12 mg or 20 mg to nothing? Obviously a bit longer, but I mean aside for that, since you would have to account for the additional day or two for the half-life thing to eliminate it, would there be a difference not accounted for by that mechanism, and if so why??

I don't think they are stupid questions at all, I am interested in the answers too!

I would assume some of the tolerance thing is simply based on individual body and brain chemistry but I do wonder if there are portions of it that can be explained or generalized above and beyond that? Anyone know what factors contribute?

[Richard_smoker]

well... hmm, if you went from 2mg down to 1mg then jumped off, your tolerance would recover faster than the 20mg down to zero scenario.

and you're right it would recover because of the lower levels of steady state concentrations--mostly. after 3-4 half lives jumping off at 1mg, your concentration of drug would be 1/2/2/2/2=1.0mg-->.5mg-->0.25mg-->0.125mg-->0.0626mg after 4 half lives (6 days) from 1mg jump.

whereas with the 20mg jump, you'd go from
20mg-->10mg-->5mg-->2.5mg-->1.25mg in 6 days.

with the 20mg jump, you've got more drugs still in your system on day #7 or #8 than you do on day #1 jumping off 1.0mg.

-DICK