General Pharmacological Information:

Bupe has a slow onset of action, with peak effects taking place in approximately 100 minutes. (Suboxone full prescribing information.) The peak effects for methadone take place in approximately 120 minutes (VERIFY.) The onset of action for bupe is approximately 30-60 minutes.

The duration of action depends heavily on the dosage. At a low dose (~<4mg), it is approximately 8-12 hours. At a high dose (~>16mg), it can last approximately 24-72 hours (and thus the reason less than daily dosing is possible.)

Bupe readily crosses the blood brain barrier, and is highly lipophilic.

Bupe is about 10x more potent IM than PO (oral), which is about the same ratio as morphine. You CAN eat bupe, although there is no reason to do so.

Sublingual absorption varies greatly, and can be anywhere from 25%-75%. ( ) The same percentages can be applied to an IM/SL potency comparison. However, in most people, their personal variation from one dose to another is low. (Subutex full prescribing information).

A comparison of bupe to 'done for respiratory effects found that bupe had a much higher incidence of respatory depression *not* requiring medical intervention. Bupe can cause respiratory depression, but *very* rarely anything resembling life threatening. Both drugs decreased 02 saturation to the same degree. The chances of severe respiratory depression are increased via the injection route. (Suboxone full prescribing information).

Bupe is a very safe drug for an opioid. Overdose is very difficult, even for opiate niave individuals. (Subutex full prescribing information).

See "Bupe and Dose" for further information on this topic.

Buprenorphine is approximately 96% plasma bound, primary to alpha and beta globulin (Subutex full prescribing information).

Bupe has a mean half-life plasma elimination of 37h (this can greatly vary between people) (see metabolism for further information) (Suboxone full prescribing information.) The half-life of methadone is 15-22 hours, although recent data suggested this could increase with repeated administration, and be as high as 150 hours.

Note about Suboxone: The Naloxone is present in a 4:1 ratio in both dosage strengths (8mg/2mg and 2mg/0.5mg). See "Subutex vs. Suboxone" for further information on the naloxone component.

Metabolism:

Buprenorphine undergoes N-dealkylation into norbuprenorphine and glucuronidation. This is done by the cytochrome P-450 3A4 isozyme (Subutex full prescribing information.) Norbuprenorphine is an active opioid. It is similar to bupe from what is known of it, which isn't much. From one in vitro test, it has a very similar affinities to bupe. Norbupe is a full agonist at delta and ORL1 with a low potency, but bupe antagonizes it's effects. This study also states that at the ?- (mu?) and Kappa- receptors, both bupe and norbupe are potent partial agonists, with bupe having a low effacacy and norbupe having a moderate effacacy, which we know is not true (in terms of kappa), and makes me doubt this study. (Huang et al., 2001) Further studies are necessary, or more access to information for me.

NOTE: Whether you take it orally or sublingually, approximately the same amount of norbuprenorphine is bioavailable. If, for some reason, you would want to maximize norbupe and minimize bupe, oral would be the way to go. This shows that the first-pass liver breakdown is responsible for the low oral availability of buprenorphine, quite similar to morphine. This also hints that *possibly* the reason for IV use resulting in a better high being the minimization of norbupe, but that is pure speculation.

Inhibiting/Inducing P450 3A4 will cause differences to you personally on how bupe works. What those changes would be are impossible to say without further investigation. Unfortunately, this includes HIV protease inhibitors, just like 'done. It is doubtful any significant differences/problems would arise that dose adjustment wouldn't solve.

NOTE TO CHEMISTS: There are several direct derivatives of bupe that are of much greater potential for use for pleasure, certaintly worth a try to *experienced* people. I imagine this could be difficult, due to bupe's complex structure. I'd like to find out more information about this.

Pregnancy:

Bupe is very similar to mdone when it comes to pregnancy. The good part, however, is that neo-natal withdrawals are less, for obvious reasons. (Fischer et al., 1998) Bupe also being the unique drug that it is that very rarely causes tolerance would be less likely to cause problems related to neo-natal addiction later in life if such problems do indeed exist. I have not backed this up, nor has problems later in life have been confirmed (making this impossible to back up,) this is mostly assumption and logic. I am fairly certain if you become pregnant or are planning on becoming pregnant it will be recommended you switch to bupe, if this didn't require a major dose reduction. This, however, is 150% better told to you by a doctor, and a decision made with his advice.

Partial Agonist?:

Buprenorphine best classified as a mixed partial agonist-antagonist. Does the fact that it's a mixed -antagonist make it weaker? Nope, in fact if anything it's a good thing (that it antagonizes, or rather doesn't agonize, kappa.)  Does the fact that it's a *partial*-agonist? Yes. They are two different things as far as Buprenorphine's classification is concerned. Bupe is a *very* bizarre drug, mostly due to the fact that it's a partial agonist.. I can't emphasize this enough. It has a ceiling for agonist effects (due to it's partial agonist nature), and, for example, 16mg is not twice as strong as 8mg.

Bupe can also be classified a mixed antagonist at mu because it has a very high affinity, which means it pushes whatever is there off of the receptor and takes it's place, and it's partial agonist nature (low efficacy, to put it simply) means it can't do the job that was just being done. This can cause it to be classified as having mixed -antagonistic effects, however partial agonist is a better classification as long as the dose is proper. It doesn't simply have a "low efficacy", it's better put as a "partial agonist." Read on for more theories on this.

Taking a large enough dose of bupe, out of proper clinical dosing, can be enough to do a UROD, as it pushes all the opioids out of your brain (VERIFY AND PROVIDE REFERENCE). This is what causes the problem with starting bupe. You have to go through some withdrawals. See the part on starting buprenorphine and methadone vs. buprenorphine for further information.

So what exactly does all this mean? It is easiest (and still largely accurate) to describe buprenorphine as a normal opioid agonist with a sliding ceiling (by sliding I mean different in every person, and dose and effects aren't linearly linked.)

See the section "Partial Agonist Theory" for more information on what exactly a partial agonist is, in theory (and in practice.)

Bupe and dose:

Bupe is a very weird in one regard when it comes to dose. As I already explained, double the dose doesn't equal double the effects. The reason for this is because as the dose goes up the efficiency goes down. (1) The reason for this is unknown, and related to partial agonist theory. I honestly wish I knew.

Dose for highest efficiency: 0.3mg (IM.) At this dose, it's effects are maximized and it behaves almost completely like a full agonist, acting equal to 10mg IM morphine in opiate nieve individuals. (Buprenex full prescribing information).

32mg is about the ceiling level. This ceiling level is different in every person (see bottom of this section.) For this reason, it is *possible* that in people who have a very low ceiling are those that would likely fail at buprenorphine, but further information is necessary. Increasing the dose higher than this will have the loss in efficacy overtake this increase in amount in your system. Taking doses higher than the ceiling will eventually lower it's effects, and taking very high doses will function as a straight up antagonist, (1) although again more information is necessary. (see below).

There is one study to this regard available, in rats a dose of about 1mg/kg caused an end to increase in agonist effects and a linear reversal in effacacy. In the average human this would be a dose of about 80mg, which is way more than ~32mg. Obviously, since it's a different species, the numbers can't be applied. It does seem however that this same mechanism happens in humans, but at a lower dose. Further studies are necessary. (VERIFY AND PROVIDE REFERENCE)

An 8mg-24mg dose is highly suggested for maintenance, depending on your personal reaction to the drug and dose. If you go over 16mg, I STRONGLY suggest you take it more than once a day.

It is also important to say that 32mg is the *GENERAL* ceiling. This depends on the individual, but in every individual a ceiling was reached, and usually above 8mg. (Subutex full prescribing information.) So please remember, more doesn't necessarily mean better with buprenorphine. If this is the drug for you, you will find the proper dose, and don't feel like you are getting gyped because you are only on 8-24mg.

Tips for getting the most out of bupe: (This is one of the reasons I kept emphasizing this. I wanted to make sure people knew how to get the most out of it.)

1. First and foremost, see "bupe and dose" in the above section.

2. Cut your dose in half, and take it twice a day. This is because of efficacy as I just explained. By taking it twice, you get more bang for your buck, and it's long half-life makes sure that it's effects are cumulative the second time you take it. I strongly believe this makes a big difference. However, for you, as always, it could be different. Certaintly worth a try, and definetely if your dose is over 16mg daily, or if it's just not working and you've reached the ceiling.

3. Take your dose in the evening. I have personally found that when I take it in the morning, it leaves me wanting more and having very little effect. If I wait it out and take it later in the day, it works great. Granted, I have to be a *little* sick for about an hour or two, but it's nothing really, for me at least.

4. Hold it under your tounge for longer than 15 minutes. At first it didn't take as long as it does now, it took about a half hour (to ABSORB, not to DISSOLVE.) Nowadays it takes at least an hour for it to absorb as best as it will. SL absorption varies greatly from individual to individual, which is one possible reason why bupe works for some people and not for others.

How can I tell that it's absorbing and how long it takes? I have been taking this drug for several years. I can feel it tingle on my tounge. I can taste the drug in my mouth. If my tounge is in it, it will tingle. If I take my tounge out before it's done, it will stop tingling to some extent. This is how I can tell.

You have nothing to lose by trying.

I will add more as I think of them and find out about them.

Partial Agonist Theory:

A very fascinating section coming soon. This may help to explain the reasons bupe works the way it does, and may even in the future help to find a way to maximize the drug's effacacy. (Not my summary, the theory itself).

Buprenorphine, Withdrawals, and Detox:

There are two aspects to this, withdrawals when switching to bupe and withdrawals from quitting bupe.

Withdrawals from switching to bupe:

You do have to go through at least a little withdrawals if you are addicted to opiates. This is unavoidable. Now, if you are switching from heroin, it really isn't that bad. See "General rules for starting buprenorphine" for further information.

Buprenorphine withdrawals:

Bupe withdrawals are mild at best (in comparison to other opioids.) For this reason, it is a great thing for people wanting to get off 'done but unable to deal with the withdrawals. Unfortunately, due to it's long receptor half-life like 'done, the withdrawals will last at least a month (although this too is individualized, and can be shorter.) Bupe has one major unique symptom of withdrawal that will be the centerpiece: this unbeatable fatique that will outlast all the other symptoms. All of the other symptoms, except a few minor and not worth mentioning unique ones such as stomach grumbling, are similar to other opioids. I have been told that the withdrawals are the worst during the first week and then proceed to lighten up alot. Once again, individualized.

It is strongly recommended you do NOT taper your dose really low before quitting. It doesn't work, and doesn't help. It'll make the withdrawals linger much longer. It is not a good idea. Reports of withdrawals cold turkey have been much more positive than taper attempts. (PROVIDE REFERENCE) The suggested dose to go cold turkey from is 4mg. Your body will take care of the rest (via the slow dissassociation of the drug from the receptor, lasting quite a long time, creating an auto-taper.)

I must say however, as I have in just about every other section, this is individualized. There have been people who have had bad withdrawals from buprenorphine. In this case, a different strategy is warranted, *possibly* involving a longer and lower taper.

Treatment with Naltrexone (although strongly frowned upon by myself) is possible very early after the cessation of low-dose buprenorphine treatment, within days, and does not cause severe withdrawal symptoms. (Bell et al., 1999) This certaintly is individualized, and if you are in the rare situation of having bad withdrawals after stopping low-dose buprenorphine, it is a very bad idea. (ADD BELL)

 Continued in next post:

Nephalim of