bioavailability - technical

Does bioavailability refer to the total amount of a drug that is absorbed into the bloodstream? Or does it refer to the total amount that survives first-pass metabolism?

If it is the former, does that not mean that sublingual would achieve ~100% bioavailability?

Get ready for this!

For you VelocideX, I'll type out the definition and explanation

From Rang et al Pharmacology 4th Ed 2001, page 70

Bioavailability

To get from the lumen of the small intestine into the systemic circulation a drug must not only penetrate the intestinal mucosa; it must also run the gauntlet of enzymes that may inactivate it in gut wall and liver. The term bioavailability is used to indicate the proportion of drug that passes into the systemic circulation after oral administration, taking into account both absorption and local metabolic degradation.

It is a convenient term for making bland generalisations, but the concept creaks badly if attempts are made to use it with quantitative precision, or even to define it* One problem is that it is not a characteristic soley of the drug preparation: variations in enzyme activity of gut wall or liver, in gastric pH or intestinal motility, all affect it.

Because of this, one cannot speak strictly of the bioavailability of a particular preparation, but only of that preparation in a given individual on a particular occasion. Even with these caveats, the concept is of limited use because it relates only to the total proportion of the drug that reaches the systemic circulation, and ignores the rate of absorption....



* The definition of bioavailability offered by the US food and drug administration is : 'The rate and extent to which the theraputic moiety is absorbed and becomes available to the site of drug action'. You may be forgiven for finding this confusing. The double use of 'and' gives the definition four possible meanings, two of which are obfuscated by the uncertain meaning of the phrase 'becomes available to the site of drug action'.

Click to expand...

Hope that is of some help

Fantastic... does that imply that if you can avoid the intestine and first pass metabolism that you can get bioavailability near 100%? I realise IV is the only thing that gets there, but I'm curious as to how close sublingual comes.... This isn't just in relation to MDMA; i'm interested in it for selegiline tablets, dissolved under the tongue. Seems like a good way to save money, given its very low bioavailability. The catch, then is that you need to take very small amounts, and you need to be very careful about how small lest you go over the equivalent of 10mg/day oral

I'm pretty sure sublingual administration will have reduced bioavailability compared to IV. For example, from memory the bioavailability of sublingual buprenorphine is about 40-50%.
According to John Derricott (UK harm reduction specialist), the closest to IV is shafting - injecting (no needle) a drug solution up your bum so it is absorbed into the lower portion of your rectum. Apparently 3 veins drain fluid from the bowel at this point - 2 go back to the heart, 1 goes to the portal vein. So you should get 2/3 dose in about 30s (applies to water soluble drugs only)

The bioavailability of a drug depends not only on route of administration but also the drug itself so for example fentanyl has quite a high bioavailability administered sublingually/absorbed through buccal mucosa as does prochlorperazine but other drugs are poorly absorbed via this route. Not all drugs have a higher bioavailability if taken rectally compared with oral admin as depending on the molecular structure they will be more suited to absorption at different points along GI tract. Not sure what the situation is for selegiline - if molecular structure enables it to be absorbed sublingually then due to avoiding first pass metab the yes bioavailability will be greater. I will check some refs and post later if I find anything. Hope this helps

biodistribution vs bioavailability vs pharmacokinetics.

in my work, i refer to bioavailability as the ratio of the drug's usable concentration at the site(s) of primary action / total amount administerd via a given route.

btw, selegeleine's bioavailability is increased 4x w/concurrent food administration, and from many years of selegeline use, might i suggest decresing the dose to 5 mg every 2nd day or 2.5 mg/d.

FYI:

Monoamine oxidase inhibition by L-deprenyl depends on both sex and route of administration in the rat

NEUROCHEM. RES. (USA), 1993, 18/12 (1299-1304)


The monoamine oxidase B (MAO-B) inhibitor L-deprenyl, widely used to treat Parkinson's disease, has frequently been studied in animal models. We have examined the effects of several variables on activity levels of MAO-A and B in rat brain and liver following chronic (3 wks) treatment with L-deprenyl. Significant effects were observed for sex (females showed lower overall MAO- B activity in the liver), dose (MAO-A and B inhibition increased with dose, with females exhibiting greater sensitivity), route of administration (subcutaneous injection was more efficient than oral dosing), and dosing interval (MAO-B was significantly inhibited when dosing interval was increased to as long as 168 hours). Our results thus indicate that the effectiveness of L-deprenyl in vivo is dependent on several factors and that these must be taken into account in studies involving the benefits or risks of this drug.



Slow recovery of human brain MAO B after L-deprenyl (selegeline) withdrawal

SYNAPSE (USA), 1994, 18/2 (86-93)


L-Deprenyl (Selegeline) is an enzyme-activated irreversible inhibitor of monoamine oxidase B (MAO B; EC 1.4.3.4). It is used to treat Parkinson's disease at a dose of 5 mg twice a day. Since enzyme inhibition is irreversible, the recovery of functional enzyme activity after withdrawal from L-deprenyl requires the synthesis of new enzyme. We have measured a 40 day half-time for brain MAO B synthesis in Parkinson's disease and in normal subjects after withdrawal from L-deprenyl. This is the first measurement of the synthesis rate of a specific protein in the living human brain. L- Deprenyl is currently used by 50,000 patients with Parkinson's disease in the United States and its use is expected to increase with reports that it may be beneficial in Alzheimer's disease. The slow turnover of brain MAO B suggests that the current clinical dose of L-deprenyl may be excessive and that the clinical efficacy of reduced dosing should be evaluated. Such an evaluation may have mechanistic importance as well as an impact on reducing the side effects and the costs arising from excessive drug use.

I've used 5mg/day for three weeks before and encountered no problems. You believe 5mg every other day will be as efficacious?

It's annoying there's relatively little work in healthy adults to determine % MAO-B inhibition... given that MAO-B increases with age.

I am aware of the bioavailability increase with food.

5mg/d is fine - for the most part, unless you indulge in other strong psych activators - in which case, get used to unpredictability.

over the long term, i found cognition enhancement decreased only marginally w/a decrease in dose from 5 to 2.5 mg per diem while alleviating most of the peripheral symtomatics that were becoming evident after 3+ months of use at 5mg p/d.

selelgiline, i am coming to believe, is a tricky bastard where less is more may be the way to go.

for that matter, i am becoming rather cautios w/any pharms that directly affect medium to long term homeostasis, and specifically enzymatic inhibitors of all types, be they MAO, AChE, BuChE or whatnot.

and dont get me started on the neurotransmitter reuptake inhibitors, the full aftermath of whcih we have yet to experience.

I dont intend to use for 3 month periods.... more like 3 week periods for exam cramming