Peak plazma leveling for methamphetamine? Differences and implications.

[DJHENRU]

Im not sure if this is basic/other/advanced or what.
What does it mean when different routs of administration have the same amount of time that peak plasma levels occur?

In regards to methamphetamine, I read in one study ingestion and smoking both peak at hr 2.
This was "because smokers have inhaled vapor that still is taken through the body like ingestion, but through the mucous membranes of the respiratory tract."
Is this still correct with Iv or other ROAs? I began to think could it's metabolites play any significant role at all?

I know there are variables within drugs for ROAS changing bioavailability, and that their active routs are not all linearly the same potency or excretion rate, I'm just wondering about a bit of clarification for methamphetamine.

Cant remember the reference but it seemed a bit dated of a study published by the DOJ I think but it cought my attention hosted on some Mexican domain thus I cant find it easily now...

 

[pasha]

What does it mean when different routs of administration have the same amount of time that peak plasma levels occur?

Plasma levels of any drug basically means the concentration of the given drug in your blood. Peak-plasma-levels means the amount of time it takes a drug to reach its highest concentration in your blood. So if two different methods-of-administration reach peak-plasma-levels at the same time, it means the highest concentration the drug can possibly reach has been achieved at the same time.

In regards to methamphetamine, I read in one study ingestion and smoking both peak at hr 2.
This was "because smokers have inhaled vapor that still is taken through the body like ingestion, but through the mucous membranes of the respiratory tract."
Is this still correct with Iv or other ROAs?

Methods-of-administration can play a significant role in peak-plasma-levels, even though it differs from drug to drug. Generally though, since the methods-of-administration other than oral bypass first-pass metabolism, they will most likely achieve peak-plasma-levels faster.

I know there are variables within drugs for ROAS changing bioavailability, and that their active routs are not all linearly the same potency or excretion rate, I'm just wondering about a bit of clarification for methamphetamine.

For this we go back to first-pass metabolism. If a drug undergoes extensive first-pass metabolism, some if the drug may get lost in the gastrointestinal tract, and/or the drug maybe absorbed poorly. The IV route has an absolute bioavailability because it is guaranteed that 100% of the drug will enter the bloodstream.

 

[DJHENRU]

hm well I did review the publication http://www.biblioteca.cij.gob.mx/Ar.../Metanfetaminas/Articulos/methamphetamine.pdf
I guess Its difference is that peak plasma levels happen at the same time, I think when metabolism begins(injection has a bit different of a scale where it peaks lowers and peaks)
Orally, amphetamine excreted is about ~15% more than smoked but these factors change(lowers with oral dosing) due to repeated administration.

 

[pasha]

I guess Its difference is that peak plasma levels happen at the same time

I didn't read the link you posted but how is that different if they happen at the same time?

Orally, amphetamine excreted is about ~15% more than smoked but these factors change(lowers with oral dosing) due to repeated administration.

It could be because orally the amphetamine lipophilicity would play a bigger role, and it would be the more likely scenario where the amphetamine binds strongly to fat compared to smoked. Hence why oral administration has a longer half-life.

What you need to do is look up the pharmacokinetics of each method-of-administration, and compare all three of them to get a more resolute picture.

 

[hatrix]

Peak plasma levels are literally when you would be peaking on the drug, the point when you would be highest because you have the highest concentration of the drug in your blood.

IVing methamphetamine should have peak plasma levels reached rather instantly, concurrent with the rush. I do believe smoking meth actually can get you higher, though that term is highly variable to the individual, but from what I've read peak plasma levels are generally higher when methamphetamine is smoked, but take longer to reach those levels then when IVed.

I'm not to sure how else to answer your question though. Chromophobia did a good job explaining anyways.

 

[DJHENRU]

Generally though, since the methods-of-administration other than oral bypass first-pass metabolism, they will most likely achieve peak-plasma-levels faster.

I am making the thread reading otherwise about this generalization. I have read that cocaine, in its freebase form and inhailed as vapor, If I recall has a potency change thats numbers didnt seem to resemble the scale of change IV has over interrectal.
I was wondering then if M-amp doesnt just go up the scale like mostly it's believed thought of with bio-availability increases with different ROAs.

...I guess stating this question sort of mixed up, that I am too freely interchanging bioavailability, peakplasma time, potency and excretion?

 

[hatrix]

I really still don't know what you mean. That generalization is true. It says why in the statement. What further needs to be explained ? I'm not understanding.

You're making it to generalized though. Not every drug is the same and has the same BA for every ROA.

 

[Swimmingdancer]

Are you misreading that study? I thought it said smoking caused peak blood levels sooner than oral ingestion, not at the same time.

 

[DJHENRU]

Are you misreading that study? I thought it said smoking caused peak blood levels sooner than oral ingestion, not at the same time.

for inhailing mamp 2.5 h, but a plateau was sustained for an additional 2 h.
for oral he time to peak was between 2.6 and 3.6 h

"The kinetics of smoked methamphetamine are quite different in character from those of smoked cocaine, which is absorbed very rapidly with kinetics similar to that of IV administration. The kinetics of smoked methamphetamine more closely resemble that of oral administration. Cook et al. [21] attribute this to subjects swallowing some of the smoked dose, absorption of drug trapped or adsorbed on the mucosa, or the drug being retained in and slowly absorbed from the lungs. This is further compounded by the long half-life of the drug"
I just wonder why people find the other ROAS so good when the disliniar numbers I see just make me always ingest.

 

[pasha]

Different methods-of-administration do not always indicate different kinetics since as I think I mentioned before, It's drug specific.

 

[hatrix]

I just wonder why people find the other ROAS so good when the disliniar numbers I see just make me always ingest.

Some people just prefer using certain ROAs, regardless of the drug. Oral methamphetamine's bioavailability is decently high (around 62% or something), but it's higher when insufflated or smoked and comes on much faster than when taking it orally. I'm sure you can see why people would prefer those ROAs, especially if they are addicted. The sooner they get higher, the better.

Plugging is also another ROA that offers high bioavailability comparable to insufflation, though higher, and a rapid onset. It's most comparable to IV.

 

[Swimmingdancer]

I read in one study ingestion and smoking both peak at hr 2.
This was "because smokers have inhaled vapor that still is taken through the body like ingestion, but through the mucous membranes of the respiratory tract."

Are you misreading that study? I thought it said smoking caused peak blood levels sooner than oral ingestion, not at the same time.

for inhailing mamp 2.5 h, but a plateau was sustained for an additional 2 h.
for oral he time to peak was between 2.6 and 3.6 h

But as you just said, that study does not say that oral administration and inhalation both cause peak blood levels at the same time. They are not both at 2 hrs, the average for inhaling was 2.5 hr and the average for oral ingestion was 3.1 hr. That is a significant difference. There would also be a difference in what that peak level was. And then the "onset", the time when you first begin to notice the drug's effects, is going to be different for the 2 ROAs as well.

I just wonder why people find the other ROAS so good when the disliniar numbers I see just make me always ingest.

Methamphetamine undergoes metabolism into amphetamine, and amphetamine is also metabolized into some pharmacologically active metabolites, so metabolites of meth do play a role in its effects. Oral administration provides much longer-lasting effects than other routes of administration. When I was using meth I preferred oral because it seemed safer, lasted longer and induced less urge to redose. People often use the ROA that they were first introduced to, the ROA that is their favourite in general for all drugs, or the ROA that will give the fastest onset (or most intense effects), rather than really making an educated choice about it. I know I've certainly done that in that past rather than weighing all the options.

Peak plasma levels are literally when you would be peaking on the drug, the point when you would be highest because you have the highest concentration of the drug in your blood.

Just wanted to point out this is not always the case. For example, in that study, the meth smokers reported peak subjective effects 18 min after inhalation, which does not correlate with the time of peak plasma levels of meth.

Different methods-of-administration do not always indicate different kinetics since as I think I mentioned before, It's drug specific.

Really? Are there actually any drugs where the pharmacokinetics are identical for different ROAs?

 

[pasha]

^ Yes there are some cases where bio-availabilities, absorption, peak plasma levels, etc are somewhat similar. For them to be absolutely identical though is impossible.

 

[Swimmingdancer]

^ Yes there are some cases where bio-availabilities, absorption, peak plasma levels, etc are somewhat similar. For them to be absolutely identical though is impossible.

Oh I see, did you just mean that generalizations such as IV>smoking>snorting>oral when it comes to specific kinetics like time to peak plasma levels are merely generalizations and not true for all drugs?

 

[pasha]

^ Yes you're pretty much almost with me. I mean that different methods-of-administration will always have different physiological kinetics. Where they pass through, how they get there. Sometimes though, but not always, the pharmacodynamics and kinetics such as bioavailability, tmax, cmax, distribution etc may be somewhat similar.

Somewhat off topic but an interesting one that tricomb and I where discussing, is the differences between rectal and sublingual benzodiazepine administration. tricomb mentioned that surface area is essential to determining absorption, so if you take the surface area of the mucosa in the colon, and that of the frenulum, it would be interesting to see if the predicted increase in abosrbtion does exist.

 

[Swimmingdancer]

^I see . I still think the OP was overestimating the similarity between inhalation and oral, that that doesn't take into account metabolites, and that similar times to peak blood levels do not mean similar effects.

 

[DJHENRU]

^I see . I still think the OP was overestimating the similarity between inhalation and oral, that that doesn't take into account metabolites, and that similar times to peak blood levels do not mean similar effects.

I can think of a few different reasons 1st pass metabolism is different.

first of all the ph excretion changes, like besides ingesting differing ph leveled foods, I wonder if there are differences in acidity changes in the gut mediated by acidity changes from chewing(it increases it) but It might not be, because of the time it takes for kidneys to create conditions for excretion rate changes.
Gluthione maybe reacts better to oxidation instead of just eventually going from the nervous system to the liver then excreted.

I also maybe noticed a greater degree of the time necessary to provoke pupil dilatation. Perhapse this is because of the serotonin in the stomach since it is always partially agonized in effect but it seemed with m-amp nieve via oral ingestion that the difference was greater between ROAs