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oldschool?
11-28-2010, 05:05 PM
Does any one know specifically (based on a link to some stat. or direct experience) if Methadone is far more bio available when injected than when taken orally.

As far as I know Oxycodone is the only opiate that has oral bio-availabilty equal to IV admin so I assume this is the case, and based on SWIMS experience I agree - but I wonder if its the same as Morphine (correct me if I'm wrong but oral only gets like 40-60% where you want it to...)

Now I have read quotes saying "peak blood levels" of methadone are reached at the same time regardless of oral or iv admin. which is pretty hard for SWIM to be live as SWIM (several someones I know in fact) inject their methadone the 6 days a week they can and has been doing so for over a year with shots that feel a hell of lot like H - of course the high doesn't last like it did years ago pre habit.

This is the problem and the reason for this whole post is that my buddy SWIM (who's far too paranoid to even post on a site like this) has been trying and failing for some time to switch back to oral use...he has gone whole years during the last 6 or more on mmt without shooting up but can't seem to shake it this time.

He's been going to the pharmacy 6 days a week again (voluntarily) but hates life so much and wakes up in mild wd every fucking day and is baffled and he's wondering "why am I craving a shot so goddam badly when I've been ingesting methadone every day."

He's ready to get his carrys back and probably could this week but I'm trying to talk him out of it...

His counselor (no medical or opiate specialist) claims that any craving can bring about withdrawl distress but SWIM finds it really hard to believe he'd get physical symptoms just because he want to inject his dose so badly but can't because he has to go to the pharmacy for it...(again this was SWIMS idea not his dr.s so he's having a pretty damn hard time deciding what to say at his Dr. Appt this week....)

bla bla bla I'm long winded as this shits been plaguing my mind all month tying to help SWIM decide what the fuck to do...some hard facts on oral vs. iv. bio availabilety could help but any other advice is also welcome

LayinLow
11-28-2010, 05:26 PM
I know methadone's BA is very high taken orally.

oxycodone's oral BA is not equal to IV administration. Oral ~ 80% , IV - 100%
Not sure what to say about your friend... tell him he's lucky to be getting methadone at all, and needs to take it like he should. Or maybe he would rather have nothing. Physical symptoms from not shooting it seems a little far fetched. He has a needle fetish, tell him to get his take homes like a big boy and shoot benadryl. Methadone shots that felt like H? You guys really like your methadone there ;)

harmonik
11-28-2010, 05:32 PM
I search and see immediately:

Bioavailability, 40-90% (oral) .... Methadone has a typical elimination half-life of 15 to 60 hours with a mean of around 22.

bioavailability is 100% if you're using IV as your ROA. I'm guessing it isn't lasting as long because if 100% of your dose is in your veins, it would be a lot quicker to leave your veins?

i've noticed with just about everything except smoking that IV has a much shorter duration... i dunno what to tell you man, do you w/d when you take orally?

OpiateQueen
11-28-2010, 05:45 PM
shooting your methadone is a fucking hard habit to break once you start doing it all the time....
I don't believe it works much better in the long run, obviously it kicks in faster, but it certainly doesn't last as long, so its weird that your friend reckons he is hanging out quicker from oral ingestion....

Maybe when he was getting take homes he was splitting the dose or having it later in the day?? How long has he given the permanent oral route this time around?? What kind of dose are we talking about??
Something like an H shot?!?! Come on... SWIM did the same for ages and unless my done was way different to yours...it aint nothing like a shot of Harry..

What kind of form do you get it in?? How much liquid do you end up having to shoot? Do you boil it down or what?

I haven't searched the bioavailability in awhile... but they always used to tell you about 90% oral BA. If it really is a range between 40-90% as someone stated above, then that is a pretty large possible variation. I'd say it would depend on a few factors.

oldschool?
12-10-2010, 02:41 AM
thanks for the advice guys and gals - all relevant

regarding iv 'done being "like H" obviously I mean similar not identical!! - I also note that I said it specifically to disagree with other posts I've read on this site suggesting that "peak blood levels were reached at the same time through oral or iv administration"

Also in comparing the effect of methadone to H my experience is pretty backwards...

My first IV opiate was mophine with no H in my hood. At some point I was offered concentrated methadone with the advertisment that it was "like H" ... I tried it and sure enough it was a heck of a lot like the good "china white" I'd smoked and snorted on 2 or 3 occasions in other parts of the county. And for several months IV methadone was my drug of choice years before having acess to H ....

so of course it sounds like I have a "needle fixation" and as fucked up as it is from my point of view (of the first times often being the most memorable or best) any decent' shot of H would bring on nostalgia for those first walloping shots of Juice free methadone that knocked me on my ass (of couse I never overdosed like from H later on...\
also shooting methadone is closer to H than morphine specifically referring to the initial rush - as in no pins n needles - smoother onset more similar to oxy or H than Morph... also take this in the context of a person who's been on methadone for 6 plus years havn't ever (maybe twice with no effect) done H in that time and living in a part of the country where there is virtually no H.

so as far as opiate use my (or swim's lol) has mostly been the methadone, some expensive dabling with Morphine but given the methadone history the methadone shots seem to feel a hell of a lot better than any morphine unless in actual withdrawl distress

your right shooting methadone is damn hard to stop and usually the doses have been split...on a weekly pick up he'd do a couple shots a day the first couple days of the week (plus the witness oral on the first day) so by the last couple days yer attempting to ration out a single shot each am which barely works and then your half dope sick a day or two at the end of each week tossing and turning so bla bla bitch bithch stop complaining and change!...easier said than done

anyhow on to 3 days a week pick up so could be able to fix daily if some degree of self control or else just be waiting for the bloody pharmacy to open 3 days a week instead of 1 like the old days...but shit its still better than the hellish last month of waiting for the pharmacy to open EVERY DAY... only 6 more hours...I'll pray I sleep through most of them

SuperJunky
12-10-2010, 03:53 AM
I shoot methedone on occasion, not a good idea, almost impossible to stop once you start, then again I have pills so they're always available. Ever heard of sleep walking? Been so fuckin stressed I started prepping and shooting large quantities of methedone while asleep. I'm kind of glad I ran out, It's scary shit to wake up in the morning and find a 10cc syringe full of blood w/ no idea how it got there. I find IV to be much more effective, I can dose once a day but get no or very little day to day build up. To dose orally I have to do split doses.

borohydride
03-03-2011, 04:13 PM
I have never injected methadone, but both the hydrochloride & the freebase vapourize very well - it's a totally different drug when used this way. Smoking 50mg, even with tolerance, had me puking my ring up (not that I minded much).

FYI I simply added NaOH powder to juice (sugar free) to crash the stuff out. OK it was a little green but it smoked OK!

Benz
03-05-2011, 07:25 PM
So you just add liquid sodium hydroxide to the methadone & the freebase separates from the liquid? Interesting, does this smoked product have the same duration of action?



Benz

Morfiend
03-05-2011, 07:40 PM
Isn't bioavailability literally the portion of the drug that reaches your veins? So how could this not be 100% when injecting into a vein for every drug?

also @ harmonik: my guess is that since 100% reaches your veins at the same time and it all leaves roughly the same time so this happens quicker... when swallowed it enters gradually and follows the "queue rule" - first in first out (lol) ... but I'm not a pharmacist so who knows

borohydride
03-06-2011, 04:46 AM
So you just add liquid sodium hydroxide to the methadone & the freebase separates from the liquid? Interesting, does this smoked product have the same duration of action?

It's shorter acting - but still like 10-12 hour buzz. I imagine the higher bioavailability when smoked (well) means you still won't hang out if your on a daily pickup. 100ml is 10 here which is pretty cheap.

Michael.
03-06-2011, 11:11 AM
thanks for that borohydride

Canis aureus
03-07-2011, 05:12 PM
I never have found bioavailabilty for smoking.. I mean, how much of the shit could be absorbed via lungs?

I could assume that bioavailabilty of oral methadone could even be higher than smoked, but when smoked it kicks in so much faster that it feels like one gets more bang of it. And because methadone's long half life, one doesn't need to take too many hits per day, if one smokes it... Oral methadone works still in the next day and one somewhat misses much of the kick of oral methadone, because of sleeping time (one could not be up all the time).

Well, as I said, I don't know about bioavailability of smoked methadone, but it seems that quite much of vapors must get out of lungs too, when one exhales (one could not hold ones breath forever).

jill
03-07-2011, 09:22 PM
Isn't bioavailability literally the portion of the drug that reaches your veins? So how could this not be 100% when injecting into a vein for every drug?

No, it's not that simple. The IV bio-availability is going to differ from drug to drug (just as it does for oral administration), it is essentially the percentage of drug that is detected in the systemic circulation after its administration.

However, the most important thing is that drugs will rarely be 100% BA IV due to several factors; losses can be attributed to immediate protein binding, an inherent lack of absorption/passage into the systemic circulation and/or to metabolic clearance.

borohydride
03-08-2011, 08:15 AM
Good points, well made Jill.

The pKa of a drug is very important since in the body it's at physiological pH which is usually 7.4 (but work with 7.1 - 7.8). The closer to that pH the isoelectric point, the more easily it passes throught the brain-blood barrier. Methadone, happily, is not very protein-bound at all BUT the pKa of it's hydrochloride is 8.25 & of it's freebase 9.2. This is why it has a slow onset. The body metabolizes methadone->normethadone->dinormethadone->imine-> which is one of the reasons the duration is so damned long. Oral bioavailability is usually cited as around 80% but thats over a lot of hours so peak plasma levels won't quite match what's expected. I expect smoking will get around 80% of it into the body - but all in 5 seconds.

Injecting it is a lot faster - but smoking the freebase is another ball-game indeed. It's onset is almost as fast as heroin & the flash lasts for ages and ages. Really, on reflection, I'm not sure if smoking it IS a good idea for most people - your almost BOUND to end up with a huge, unstoppable habit (it's that good). Still, if you can keep it's use down to annually then your most likely going to be OK. That's IF.

borohydride
03-08-2011, 08:26 AM
-DOUBLE POST-

dizzle
03-08-2011, 04:28 PM
I'm not sure if smoking it IS a good idea for most people - your almost BOUND to end up with a huge, unstoppable habit (it's that good). Still, if you can keep it's use down to annually then your most likely going to be OK. That's IF.

haha, annually, I've never met a drug addict that can think in yearly terms, hell, let alone weekly. We can all think in daily terms though......no coincidence in half-life=6-7 hours (roughly overall for most opiates).

Boro- is the reason smoking has such a quick onset- almost as fast as IV- due to the fact that when smoking freebase your smoking the -amine form and that is what the body has to metabolize it into before IV is active. Then, in the -amine form, its halflife is 36 hours (or whatever it is). So theoretically, it should hit you just as fast as IV but then just last and last.......no?

dizzle
03-08-2011, 04:44 PM
actually, I just did a search and the word "annually" has only been said 23 times (and one of those in this one) in the threads here...... in the last 5 fuckin years....... hahaha!!!!!

Just goes to show you what I said is so true, we just simply don't think in terms of years.

borohydride
03-09-2011, 09:00 AM
^Exactly. Medically, methadone is usually found as an addition salt - the hydrochloride. The salt cannot pass through the BBB (brain-blood barrier) so the body has to free it of the salt. Now, it's pKa is still surprisingly high, but it's very lipophilic (likes fat) so once it enters the brain, or other fatty tissue, it's going to stay there. This water:fat solubility ratio is called the partition coefficient & it's very important for activity. Levorphanol is another drug that's amazingly active if smoked (even with tolerance you only need a couple of mg). Alfentanil over fentanyl is an example of a material with a pKa nearer to pH 7.4 hence fast onset.

I suspect the amount that get's into the brain is actually a lot higher with smoking because after the lungs, the first place the blood goes is into the brain. The total in the body remains the same, but it's distribution is different. A good example of this effect is with the thiobarbiturate anesthetics. If you swallow the same amount as is usually injected, almost as much gets into the body but far less into the brain, your not knocked out by it.

-Binding (Ki)
-Efficacy
-Partition Coefficent
-BBB permeability
-Metabolism (how fast, are there active metabolites)

Those are the most important factors - you can see when it comes to designing a new material, it's quite an art form in it's own way. Things like mono-amines (amphetamines, MDMA and such) we know just what we are trying to target but the MOR receptor has yet to be mapped.


from this, I'm sure you can see why smoking freebase methadone is so much more euphoric & potent - it's also a compound widely available. I will do a simple method with images next time I get some methadone...

Woody Bear
03-09-2011, 02:29 PM
The IV bio-availability is going to differ from drug to drug (just as it does for oral administration), it is essentially the percentage of drug that is detected in the systemic circulation after its administration.

However, the most important thing is that drugs will rarely be 100% BA IV due to several factors; losses can be attributed to immediate protein binding, an inherent lack of absorption/passage into the systemic circulation and/or to metabolic clearance.
Your right that even if given IV, not all the drug will have an active effect, due to loss by immediate protein binding, and metabolic clearance before it has a change to get absorbed into the brain. However, bioavailability is a measure of how much unchanged drug makes it into systemic circulation (ie the veins), so if a drug is given IV, it will have 100% bioavailability.

Here's the quote from wikipedia's bioavailability (http://en.wikipedia.org/wiki/Bio-availability) page:

In pharmacology, bioavailability is used to describe the fraction of an administered dose of unchanged drug that reaches the systemic circulation, one of the principal pharmacokinetic properties of drugs. By definition, when a medication is administered intravenously, its bioavailability is 100%.[1] However, when a medication is administered via other routes (such as orally), its bioavailability decreases (due to incomplete absorption and first-pass metabolism) or may vary from patient to patient (due to inter-individual variation). Bioavailability is one of the essential tools in Pharmacokinetics, as bioavailability must be considered when calculating dosages for non-intravenous routes of administration.

jill
03-09-2011, 05:44 PM
Wikipedia isn't always correct and it contradicts itself in its own example.

That isn't what I learned in pharmacy school...I did say it was a lot more complicated than the simplistic statement made by Morfiend...but whateve...

Thanat0s
03-09-2011, 05:49 PM
Wikipedia isn't always correct.

That isn't what I learned in pharmacy school...I did say it was a more complicated than the simplistic statement made by Morfiend...but whateve..
jill you are totally correct.

as a very general rule tho,
subL>oral admin for the drugs WE ENJOY...

obv not hard and fast rules here,
but applies to the subject at hand.

EDIT:
above is correct, but offTopic.
though was a diff thread...
for water sol drugs, IV is considered the 100%BA std...

assuming PURE drug that is 100% h2o soluble you have 100% BA...

does not always work that way in practice,
and in fact some drugs are so limitedly soluble that the BA in reality is higher for oral admin than 'attempted' ROA BA...

the stats youll find online RARELY take into account that people shooting 'done are using fucking pills or syrup that are not as water sol as a pure watersol 'done compound would be...

fuzzy fucking lines,
and this is where IRL experience comes into play.

methadone is NOT worth shoot vs oral in the commonly available US forms with kitchen table prep methods...
its a measure of unchanged drug entering your bloodstream








ANY questions?

; )

The Ryan
03-09-2011, 07:47 PM
No, it's not that simple. The IV bio-availability is going to differ from drug to drug (just as it does for oral administration), it is essentially the percentage of drug that is detected in the systemic circulation after its administration.

However, the most important thing is that drugs will rarely be 100% BA IV due to several factors; losses can be attributed to immediate protein binding, an inherent lack of absorption/passage into the systemic circulation and/or to metabolic clearance.

i always thought other BA (oral/nasal/rectal) were based off of IV use being 100%.

shows what i know.

so say "drug X" has a 95% IV BA. and lets say a 45% oral BA.

if one injected 100mg of "drug X," than with the 95% IV BA than 95mg of "drug X" would be detectable in said persons system.

so if orally ingested, would the amount be 45% of the 95mg (47.3mg) that is detectable through IV admin (because i thought BA's were based off the amount of drug that makes it to your system via IV) , or 45% of the 100mg originally taken (45mg)?

doesnt really matter too much, just curious.

Thanat0s
03-09-2011, 07:52 PM
BA i think is based on amt of drug that has an 'effect' on the intended system.. no?
ive yet to see an IV = <100% but i could see how that could be the case based on how one views the drug...

ie: is IV loperamide 100%BA?

fucxors im cornfused now...

good thing im out of boozes, eh?

GOLD N DIEMONDS
03-10-2011, 12:11 AM
!
!
!
THEE BIOAVAILIBTY OF ANY DRUG GIVEN IV WILL ALWAYS BE 100%
IV BA OF DRUG = 100%

This is simple the standard definition of BA-
the definition does NOT change because of the drug
ryans example is a great example of why the MUST be a 100% to work from.

Then you have---Absolute bioavailability
and -------------Relative bioavailability

and yes JILL, that where things get really fucking complicated
<3



/
( ok I like IV + 100% ;-)

borohydride
03-10-2011, 06:05 AM
Technically, bioavailability is the % of the UNCHANGED compound that reaches the blood. That's why for CNS activity it's not the whole story. A large proportion of heroin is converted to 6-MAM or even morphine before it enters the brain, for example. Methadone, being a pretty hardy molecule, just keeps accumulating in the blood when taken orally so that it's very efficient when swallowed. Of course, getting it all into the brain is what actually matters. The best example I can think of is derivatives of oxycodone. There are some very potent analogs (esters at the 14 position) but it's still the bare hydroxyl that does the MOR binding). Esterification means that the glycoproteins can transport it across the BBB much more efficiently then de-esterification in the brain leaves the active material. Yhe cinnamyl ester is about x114 more potent in spite of the fact that it's still oxycodone getting you high...