Please help me lethal dose and nanograms of fentanyl.

[Kimi#4321]

Pharmaceutical Fentanyl comes as a solution for injection (Sublimaze), for transdermal delivery as a patch (Durogesic), as a tablet designed for buccal administration (Effentora) and as a nasal spray (PreFent). What is common here is that they are all designed for what is termed 'parenteral administration' which simply means not via the gastrointestinal tract. You cannot swallow fentanyl. Or rather you can, but it's bioavailability is described as 'sparse' in (chronic) studies i.e. it does not work, or at least not if one's liver is at all healthy. Fentanyl has an extremely short duration of action given that it's plasma half-life is about 18 minutes.

I won't bother you with the exact reasons for this, but I think what is important here is that whoever made this counterfeit pill relied on the user 'abusing' the pill i.e. by administering it via a parenteral route. As I understand it, imitation OxyContin makes up the bulk of these 'fakes'. Most users will crush and snort them. The serious problem here is that while oxycodone (the active drug in real OxyContin) is about twice as potent as morphine, fentanyl is around 80 times as potent. That means to approximate a 30mg OxyContin (for example), the maker of the fake would need to put less than 1mg of fentanyl into each pill.

While one might assume that these manufacturers would put the minimum amount of fentanyl into each tablet to maximise their own profit, the fact is that fentanyl is so incredibly cheap given it's potency, the trend is to put more in so that people develop tolerance and dependence. Needless to say, there is no quality control, no pharmacovigilance and given what they are doing, no concern for the end user whatsoever. They are sold by dubious pharmacists in Mexico and India. The buyer would not be aware that the medicine they purchased was fraudulent; they would not realise that they were dealing with a criminal.

The serum concentration for analgesia is around 1-2 ng/mL and around 10-20 ng/mL for anaesthesia. The latter dose regime is only used by specialists and only when mechanical ventilation and related life-support equipment is on hand. The mean concentration of fentanyl found in accidental overdose victims is 26.4 ng/mL (range 11.8-95.8 ng/mL).

I home you understand that my post is dispassionate in the attempt to provide you with the information that is useful to and understandable by you. All the data has been derived from multiple medical sources and is correct to the best of my knowledge. There are many different figures assigned to fentanyl. I think it is the order of magnitude that is important.

I have no idea under what circumstances this accident occurred so I cannot make any comments regarding this specific case. I merely wished to present what is available in textbooks, medical literature and such information as is made available to potential prescribers of medicines in which fentanyl is an active ingredient. There is a huge mythos surrounding ALL drugs but psychoactive drugs in particular and drugs of abuse specifically. Every case is unique and it is not useful to comment on specific cases.

If their is any indication as to who supplied these tablets, stopping them could be of great benefit to unwitting consumers. It goes without saying that there will almost certainly be many more of these fraudulent pills in circulation and that nobody knows if they have a pill that came from the same batch or even the same die (tablets are cast in dies, I am not making light of this terrible situation).

Thank you so much this is what I was looking for but could not find the words to articulate. The mean dosage found it accidental overdose. I appreciate you reply and the information you supplied has helped me more then you know.

 

[Kimi#4321]

@Kimi#4321 I'm so sorry this happened to your daughter. Rather than getting wrapped up in the chemistry of all this, I think time would be well spent trying to pinpoint from whom she got the pills and making sure that person sees justice served.

Have the authorities been helpful at all? It sounds like you have it narrowed down to two individuals. Have either of them at least been questioned by law enforcement? Are you aware of any type of ongoing investigation taking place?

Thus is why I am trying to figure this out the detective wants to close the case even though he knows they the people in the house adults 10 year her senior are lying. He's been on the force 25 plus years done swat and gang task force I don't see why he says he can't get the info he needs there where laws broken even before her death. So this is ultimately why as I have been on this since her passing. The system failed me I failed my daughter the system failed my daughter and I'm so over laying down and taking it.

 

[Feretile]

It SAYS Buccal in the title. That MEANS it's absorbed through the cheek, not swallowed! I specifically noted buccal administration. Any that enters the GI tract does not enter the CNS - if you don't understand, please do not post.

I've posted a link to an experiment showing that fentanyl is not orally active. Sublingual, buccal, nasal; yes. But oral no.

 

[Phobos]

It SAYS Buccal in the title. That MEANS it's absorbed through the cheek, not swallowed! I specifically noted buccal administration. Any that enters the GI tract does not enter the CNS - if you don't understand, please do not post.

I've posted a link to an experiment showing that fentanyl is not orally active. Sublingual, buccal, nasal; yes. But oral no.

If you take the time to actually read the damn paper, you will see that they test and compare oral ingestion as well as buccal and IV, regardless of the title.

I took the time to go through the paper you posted and there is no mention whatsoever of the study's results, they just list the conditions of the study.
So please post a link to a complete version of the study?

 

[Feretile]

Following that link, I could not find any results, just the conditions of the study.
If you look at the Figure 1 in the link I posted, you will see that oral Fentanyl reaches the bloodstream without being fully metabolised so it does survive first pass, although the low bioavailability (just 35% ) suggests that yes, it is extensively metabolised by the liver as you say.
Wikipedia list a similar oral bioavailability, 33%.

Edit: Here is another link to the same paper, the first one seems to not work properly: Single-Dose Pharmacokinetics of Fentanyl Buccal Soluble Film

Yes I did & it uses the term 'oral transmucosal' It REPEATEDLY uses the term 'oral transmucosal'. That is simply a blanket term for buccal, sublabial & sublingual. The drug is being absorbed by the mucous membrane of the mouth, a parenteral route of administration. Oral administration means that the drug is swallowed and absorbed through the gastrointestinal tract. The point is, it isn't being swallowed so it does not undergo first-pass metabolism by the liver & duodenal microsomes. That is why doctors write P.O. on prescriptions 'per os' meaning 'through the mouth', not 'in the mouth'.

I did go into some detail as to why oral formulations of fentanyl have not been developed. How a study of chronic oral administration failed to produce therapeutic levels of the drug in the bloodstream. So low were the figures that the CI lead them to describe activity as 'sparse', so low (and varied) were the levels.

If you please read and understand, it would save others a great deal of effort. I even explained why it was not orally active and even went as far as explaining why a fentanyl analogue designed to be orally active was never developed. I think I put quite a lot of work in to checking each item. I did check about 30 technical papers, I just did not believe anybody else would play through 30 references even if they were provided.

From a medicinal chemistry perspective, it's obviously not going to be orally active. I did specify the liver enzyme class. I gave you every piece of data in a format that did not occupy 25,000 words.

 

[Phobos]

Yes I did & it uses the term 'oral transmucosal' It REPEATEDLY uses the term 'oral transmucosal'.

You did not read the whole thing then, because if you do you would have seen this

Injectable fentanyl citrate (200 µg) administered by intravenous infusion, injectable fentanyl citrate (800 µg/16 mL) administered orally, and fentanyl buccal soluble film (800 µg) administered as a single film and as four separate 200 µg films simultaneously.

and this

The absolute bioavailability of fentanyl from the buccal soluble film treatments was 71%, which is approximately double that after oral administration (35% ). The percentage of an administered dose absorbed through the buccal mucosa was calculated to be 51%.

and this

Each subject received the following four study treatments on days 1, 4, 7, and 10: injectable fentanyl citrate 200 µg administered via an intravenous infusion pump over 5 minutes; injectable fentanyl citrate 800 µg/16 mL administered orally via a 20 mL oral syringe followed by 90 mL of water; fentanyl 800 µg as a single film applied to the buccal mucosa; and fentanyl 800 µg administered as four separate 200 µg films applied to the buccal mucosa within a 2-minute period.

I'm sure that there are very good reasons why there are no oral Fentanyl formulations, but that it's not orally active is not one of them.

 

[Nas47]

It SAYS Buccal in the title. That MEANS it's absorbed through the cheek, not swallowed! I specifically noted buccal administration. Any that enters the GI tract does not enter the CNS - if you don't understand, please do not post.

I've posted a link to an experiment showing that fentanyl is not orally active. Sublingual, buccal, nasal; yes. But oral no.

Simmilar in this manner to bupre.Low oral bioavailability.First-pass metabolism extensive.No oral forms for both drugs.Transdermal form for both too.Think there bupr.oral BA is around 10 percent.Don't know about fent,but there is too some oral activity..low,but present.Fent buccal is around 50 percent,same for bupr.buccal films,sublingual around 30...but this can vary from person to person

 

[Kimi#4321]

Simmilar in this manner to bupre.Low oral bioavailability.First-pass metabolism extensive.No oral forms for both drugs.Transdermal form for both too.Think there bupr.oral BA is around 10 percent.Don't know about fent,but there is too some oral activity..low,but present.Fent buccal is around 50 percent,same for bupr.buccal films,sublingual around 30...but this can vary from person to person

So would she have swallowed the pill. I know she did not use iv when I asked medical examiner they said they are unsure of ROA between smoking or swallowed the pill they call MEXI I have not known of anyone swallowing them however medical examiner says they found them in her backpack with a water bottle nothing else mind you these people didn't call anyone until she was gone plenty of time to clean up and come up with story she took them to sleep

 

[JTemperance]

Pressed fentanyl pills tested by the DEA in 2019 contained an average of 1.7mg of fentanyl per tablet. However, there were 29 samples (out of 106 total) with >2mg – what DEA considers a "lethal dose" of fentanyl – and the strongest pills tested at more than double the average (3.6-4.2mg).

By comparison, the average in 2017 was 1.1mg per tablet. If the upward trend in strength has continued, even at a slower pace, the average pill is likely to have more than 2mg of fentanyl at this point. And if the variability is still as it was in 2019, some pills will likely end up in the 4-5mg range.

 

[Feretile]

There is no explaining to some people. Yes, buprenorphine is another good example. In fact, it's exactly the same liver enzyme that prevents both buprenorphine and fentanyl from being orally active. First-pass will vary due to expression of the enzymes but you need a CI of about 5% to get a reliable plasma level for therapeutic activity.

I've seen people mistakenly swallowing sublingual buprenorphine and the result is just nothing happening. You cannot end up with someone overdosing. Imagine IF some madman produced true oral fentanyl.... 8mg tablets. If you simply held them in your mouth, the outcome would be very bad indeed.

 

[Nas47]

So would she have swallowed the pill. I know she did not use iv when I asked medical examiner they said they are unsure of ROA between smoking or swallowed the pill they call MEXI I have not known of anyone swallowing them however medical examiner says they found them in her backpack with a water bottle nothing else mind you these people didn't call anyone until she was gone plenty of time to clean up and come up with story she took them to sleep

Sooo sad.Sorry for your loss...what i could say...Yes I think,that she could just swallowed the pill....or just hold it under the tongue for a few minutes and than swallowing...God knows..Always said that this in America/Canada it's not normal with this fent analogues all around....yes I am a thousand miles away,but this make me feel sad.

 

[Phobos]

There is no explaining to some people.

This seems to apply to you.
I followed the link you provided to back up your statement but there are no results in there.
I provided a link to a paper where the researchers found Fentanyl to be active when swallowed, with a BA of 35%.
You claimed to have read it but you have not, as you somehow missed all the parts that mention how Fentanyl is orally active.
I quoted the relevant sections here but you provided no answer to that either.
@OpiateKiller here has told you that he knows people that have died by swallowing Fentanyl pills.
Here is a link to a case study where a guy needed Narcan after swallowing 2 Fentanyl patches:
Management of an Oral Ingestion of Transdermal Fentanyl Patches: A Case Report and Literature Review
Here's a relevant quote:

If the entire reservoir contents of one fentanyl patch were ingested, approximately 1680 micrograms would enter the systemic circulation. Assuming a 25% reduction for cross-tolerance, this fentanyl dose is equivalent to 126 milligrams of intravenous morphine

Now I have nothing against you personally and I would love to be wrong about this and happy to let it go if it was something else, but claiming that Fentanyl is not orally active when it clearly is (even though it has low oral BA) is potentially dangerous misinformation.

 

[OpiateKiller]

There is no explaining to some people. Yes, buprenorphine is another good example. In fact, it's exactly the same liver enzyme that prevents both buprenorphine and fentanyl from being orally active. First-pass will vary due to expression of the enzymes but you need a CI of about 5% to get a reliable plasma level for therapeutic activity.

I've seen people mistakenly swallowing sublingual buprenorphine and the result is just nothing happening. You cannot end up with someone overdosing. Imagine IF some madman produced true oral fentanyl.... 8mg tablets. If you simply held them in your mouth, the outcome would be very bad indeed.

He literally just highlighted and posted fentanyl in that study is 35% effective. Many pills have oral bioavailability around 30-50%, so it’s entirely normal. Obviously drugs aren’t going to be absorbed even close to 100% unless injected.

 

[Nurse Ratched]

Can y'all not argue about who is more right about the buccal, oral, anal. and nasal qualities of fentanyl on this woman's grief thread. Thank you.

Posting articles is fine if you want her to understand the nature of the drug that killed her poor Daughter but arguing among yourselves is not needed.

 

[HydroJesse23]

There is no explaining to some people. Yes, buprenorphine is another good example. In fact, it's exactly the same liver enzyme that prevents both buprenorphine and fentanyl from being orally active. First-pass will vary due to expression of the enzymes but you need a CI of about 5% to get a reliable plasma level for therapeutic activity.

I've seen people mistakenly swallowing sublingual buprenorphine and the result is just nothing happening. You cannot end up with someone overdosing. Imagine IF some madman produced true oral fentanyl.... 8mg tablets. If you simply held them in your mouth, the outcome would be very bad indeed.

I agree. Some people will just never understand things. Especially the whole taking a sub too early because your sick and then once that sub kicks inn itself worst.
In my opinion with this some
People just won’t understand unless they go through it themselves. Actually experience it themselves instead of just reading a bunch of shit online then acting like you know what your taking about because you’ve read 60 posts of people talking about what the withdrawals are like or what it’s like to take a sub to early.

 

[HydroJesse23]

Fentanyl is entirely orally active I’m not sure what you’re getting at? I know plenty of people who have died from oral use of fake Percocet 30 mg pills, the little blue ones Kim is definitely talking about.

Most fake 30s contain around 1 mg of fentanyl per pill, which to a non opioid tolerant individual can be entirely lethal, even when taken orally.

If fentanyl didn’t work orally kids wouldn’t be dying from it.

@Phobos he’s wrong don’t worry

If there was a form of fentanyl that was activated and absorbed into your body
Via your mouth the smallest amount would be killing new users. Not this 1mg to 1.5mgs those numbers are almost always based off people shallowing said drug. That’s how the state and government work when doing these studies. They hardly ever look into people using there nose or people using a needle and if they do look into IV users then it’s a completely different paper and experiment. IV users always have and always will be grouped together on there own separate from people swallowing said thing. Or even just even one else. Including snorting, eating, dissolve in mouth and anally. IV use will always be separate no matter what. There’s waaaaayyyyy too many outside factors to even begin grouping IV users with everyone else. The numbers would be literally all over the place.

 

[HydroJesse23]

Fentanyl is entirely orally active I’m not sure what you’re getting at? I know plenty of people who have died from oral use of fake Percocet 30 mg pills, the little blue ones Kim is definitely talking about.

Most fake 30s contain around 1 mg of fentanyl per pill, which to a non opioid tolerant individual can be entirely lethal, even when taken orally.

If fentanyl didn’t work orally kids wouldn’t be dying from it.

@Phobos he’s wrong don’t worry

Also these people you know of dying from these dirty 30s...
I can almost guarantee none of them are chewing then shallow or just simply shallowing them. But the ones that do and die from it or overdose and are saved I bet every single time they thought it was a narco and never expected to be given fentanyl just pressed to look like a 3

 

[HydroJesse23]

Yes I did & it uses the term 'oral transmucosal' It REPEATEDLY uses the term 'oral transmucosal'. That is simply a blanket term for buccal, sublabial & sublingual. The drug is being absorbed by the mucous membrane of the mouth, a parenteral route of administration. Oral administration means that the drug is swallowed and absorbed through the gastrointestinal tract. The point is, it isn't being swallowed so it does not undergo first-pass metabolism by the liver & duodenal microsomes. That is why doctors write P.O. on prescriptions 'per os' meaning 'through the mouth', not 'in the mouth'.

I did go into some detail as to why oral formulations of fentanyl have not been developed. How a study of chronic oral administration failed to produce therapeutic levels of the drug in the bloodstream. So low were the figures that the CI lead them to describe activity as 'sparse', so low (and varied) were the levels.

If you please read and understand, it would save others a great deal of effort. I even explained why it was not orally active and even went as far as explaining why a fentanyl analogue designed to be orally active was never developed. I think I put quite a lot of work in to checking each item. I did check about 30 technical papers, I just did not believe anybody else would play through 30 references even if they were provided.

From a medicinal chemistry perspective, it's obviously not going to be orally active. I did specify the liver enzyme class. I gave you every piece of data in a format that did not occupy 25,000 words.

From what I know of fentanyl, if it was able to be absorbed into your blood in your mouth via under your tongue or in cheek. It would just simply be waaayyyy to strong. The doses would be so incredibly low that people wouldn’t believe it to be enough. Also people wouldn’t let it dissolve entirely and now are still in pain since the form they were given is made is be dissolved in your mouth, not absorb via the stomach. So they wouldn’t get an affect from shallowing something made to dissolve in your mouth. So then people would take extra and let this one dissolve completely and it would kill them. If they would have just taken the first one correctly and not rushed the process they wouldn’t feel the neeed to take the second.

Personally I feel it’s more so to do with how strong it would be and how little would be needed to provide same pain relief compared to if the same person shallowed it. The numbers would be completely different. Not to mention people rushing the process of it dissolving and cutting themselves short probably thinking they will still get it when swallowed then not and taking more and doing that one correctly and ok now I’m repeating myself now.....

 

[HydroJesse23]

Pressed fentanyl pills tested by the DEA in 2019 contained an average of 1.7mg of fentanyl per tablet. However, there were 29 samples (out of 106 total) with >2mg – what DEA considers a "lethal dose" of fentanyl – and the strongest pills tested at more than double the average (3.6-4.2mg).

By comparison, the average in 2017 was 1.1mg per tablet. If the upward trend in strength has continued, even at a slower pace, the average pill is likely to have more than 2mg of fentanyl at this point. And if the variability is still as it was in 2019, some pills will likely end up in the 4-5mg range.

Sounds like to me I’m doing whatever I can to increase my luck ! Make sure as many of mine as possible are on the higher side towards4-5mg lmao

Unfortunately that’s how my brain works