Pregabalin is absorbed from the intestines by an active transport process mediated via the large neutral amino acid transporter 1, a transporter for amino acids such as L-leucine and L-phenylalanine.
erm no offense but did you even read the paper that you linked? your point is true for Gabapentin from your paper "
Gabapentin absorption occurs in the small intestine through an active transport process mediated by a low-capacity amino acid transporter (LAT) primarily expressed in the upper small intestine"
for Pregablin things are different, also from your paper "Pregabalin is also transported by LAT
but, in contrast with gabapentin, seems to use additional transport systems that allow drug absorption to occur along both the small intestine and the colon " .
pubmed.ncbi.nlm.nih.gov/20818832/
"Preclinical studies have suggested that
gabapentin is transported solely by the LAT1 transporter,[12] resulting in dose-limited absorption, presumably because of saturation of the facilitated transport process.[11,13,14]
Pregabalin absorption seems to be mediated by an additional pathway, thus allowing for near-complete, non-saturable absorption into the blood"
Note though that for both drugs these statements are
for oral ROA only!
you're effectively arguing that a specific mechanism for 1 ROA then prevents a different ROA from working, that's simply not true, different ROAs can have different mechanisms and different bioavailabilities. Think about ketamine bioavailability for different ROAs as an example:- ~50% snorted v up to 90% IM v 100% IV as an example, all ROAs work, some work better than others, the mechnism of action can be different though.
the problem is there are no studies on bioavailability of pregablin via other ROAs because 1. medically 90% oral is plenty good enough so no need/point to inject it in patients 2. abuse of pregab via snorting isn't a major issue and therefore hasn't been studied. That doesn't mean snorting doesn't work....
so in summary just grab a 300mg cap of pregab, snort it and come back and tell me if it worked or not, they cost peanuts, oral bioavailability is 90% (so as I said early in the thread just eatting them is fine), but if you think it won't work snorting then there's no real risk trying it versus oral is there?
ChatGPT summary on snorting pregab.
Reports of intranasal (“snorted”) pregabalin do not contradict the role of L-type amino-acid transport in intestinal absorption. The key is that the L-type transporter is relevant to the intestine; it isn't a requirement for pregabalin to enter the bloodstream through every possible route.
Think about the difference between these two routes:
Oral pregabalin
Mouth
↓
Stomach
↓
Small intestine
↓
Intestinal epithelial cells
↓
Blood
Here, pregabalin has to cross the intestinal epithelial barrier, and amino-acid transport systems such as system L can participate in that process.
Intranasal pregabalin
Nose
↓
Nasal mucosa
↓
Blood
Now there is no intestinal wall involved.
Therefore, the drug doesn't need to use an intestinal LAT transporter to get across the nasal mucosa. The nasal epithelium has its own permeability and transport characteristics.
This is the same general principle as an injection: if a drug is placed directly into the bloodstream, intestinal absorption mechanisms become irrelevant.
But there's an important caveat
The existence of reports of people using pregabalin intranasally doesn't necessarily mean that intranasal pregabalin is well absorbed or that it produces a better effect.
The literature does document non-oral misuse, including nasal administration, but the evidence base for exactly how much pregabalin is absorbed through the human nose—and its comparative pharmacokinetics versus oral administration—is much less established than the excellent evidence for oral absorption. Reviews specifically note nasal insufflation among reported alternative routes of misuse.
And this is actually a useful correction to the mental model we've been building:
LAT isn't a universal “pregabalin entrance gate.” It's one mechanism involved in absorption across particular tissues, especially the intestine.
So you can have:
Oral:
Pregabalin → intestinal barrier → LAT/other processes → blood
Nasal:
Pregabalin → nasal barrier → blood
IV:
Pregabalin → blood directly
The drug itself hasn't changed; the biological barrier it has to cross has changed.
One other interesting point: pregabalin's oral bioavailability is already about 90% and is essentially independent of dose, so there isn't a huge amount of “missing” drug that needs another route to explain its effects.
So the answer to your underlying question is yes: pregabalin can reach the bloodstream without using intestinal L-type amino-acid transport, because L-type transport is not a requirement for the molecule to enter blood by every route.
