Can somebody please explain to me why different routes of administration (excluding intravenous) have different bioavailabilities amongst themselves for a given drug, and why they change from drug to drug? For example, why does oxycodone have a higher oral than intranasal, but amphetamine have a higher nasal than oral? This has been confusing to me for a while. Thanks.

Solubility, concentration, surface area of teh membranez. :o

Lot's of stuff that i'm too stoned to write about now.

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Don't quote me here but I'm pretty sure the reason intranasal works with amphetamines is because it enables you direct access to the bloodstream (via nasal/mucus membranes) without having to pass through and be metabolized by the liver (and losing some amp in the process).

I know that people who say others are stupid for insufflating Adderall IR ("Because it's already instant you idiot, just swallow it and be patient") are definitely wrong because I'll be damned if I don't eat 30 mg one day and snort 30 the next and get much more pronounced effects on the latter.

And for me, insufflating doesn't even reduce the duration; I still get about 6 hours out of it. Granted, I take Wellbutrin, too...

Reading a pharmacology book would make it easy to understand, but I'll try to break it down for you.

In a nutshell you have:

Absorption
Distribution
Metabolism
Excretion


Absorption is the drug getting into you through whichever ROA. Distribution is how it's transferred throughout the blood stream finally to your brain. Metabolism is enzymes and whanot modifying (breaking down) the drug. And excretion is your kidneys filtering it out of your blood stream. More on this in a sec..

Different drugs have different bioavailabilities because of their chemical structure. Some have very good lipid (read: fat) solubility, some don't. Same with water solubility. Both properties are important though. The drug has to be soluble in your blood plasma and it's also gotta be lipid soluble so it can pass through membranes, most notably the blood brain barrier.

Some drugs have different or an extra xxx chemical group or whatnot that makes them more lipid soluble. Take heroin for example. Pharmacologically identical to morphine, yet it's got 2 acetyl groups slapped on it which makes it very very lipid soluble. Goes right to your dome. Faster than morphine.

Membranes are membranes (in the simplest sense), but not all drugs can magically cross them. Membranes are semi-permeable. They only let through select drugs/chemicals/ions. They're littered with proteins which help chemicals move back and forth across the membrane. Some drugs can slide right through the membrane, diffuse right through. Others need an ion channel (which is a protein) to open. And some need to be "pumped" through (again, by a protein).

The reason IV (or intranasal, just using as an example..) has a higher availability is due to distribution and metabolism. When you eat a drug (oral) it's dissolved in your stomach and passes through your stomach/SI wall via a bunch of capillaries. The drug actually has to diffuse into the capillary through the capillary wall. ;) From there it goes to the liver. Everything you eat goes to the liver. That's where nutrients are stripped, sugar stored, etc, etc. What also happens is that drug is metabolized via enzymes [pharmacological term is 1st pass metabolism, I believe]. Enzymes break shit down (for the most part). So you lose a % of your drug right there.

Wherever a drug has to cross membranes or interact w/ enzymes that break it down your probably gonna lose some of it.

If you wanna know more a pharm book would do it...

yr nose is a cave monster whereas yr gut is a super sonic terrorist

did you even stop to think about it for a goddamn second? holy fuck you must be completely retarded if you couldn't come up with at least a reasonable guess.

i am also very furious!!!!

jk, distortions a dumbass that just likes to get mad about everything.

this is a great thread, that i have learned much from in the few posts that have been made so far. thank you, madfast, for creating this thread.

The reason IV (or intranasal, just using as an example..) has a higher availability is due to distribution and metabolism. When you eat a drug (oral) it's dissolved in your stomach and passes through your stomach/SI wall via a bunch of capillaries. The drug actually has to diffuse into the capillary through the capillary wall. ;) From there it goes to the liver. Everything you eat goes to the liver. That's where nutrients are stripped, sugar stored, etc, etc. What also happens is that drug is metabolized via enzymes [pharmacological term is 1st pass metabolism, I believe]. Enzymes break shit down (for the most part). So you lose a % of your drug right there.


I followed you alright until here. If my understanding is correct, IV should always have the highest bioavailability because whatever you're injecting goes straight to your bloodstream. Intranasal bioavailability, however, is not always higher than oral. That's the part I don't quite understand. Amphetamine has a higher intranasal bioavailability than oral, but oxycodone has a higher oral than intranasal. Is this because one ROA is more efficient with fat soluble compounds, and one with water soluble compounds? Amphetamine and oxycodone are both water soluble. Is the difference due to different levels of solubility? Which ROAs are most effective with fat soluble compounds? Which with water soluble compounds?

And lastly, what exactly is it about amphetamine that keeps it from diffusing through stomach/intestinal capillaries as efficiently as oxycodone, and what differentiates those capillaries from the ones in the nose, aside from location?

Thanks. You're being very helpful.