Sublingual oral minoxidil: bioavailability and haemodynamic side effects

[Lurker otto]

The theory is that sublingual minoxidil cause less hemodynamic effects because it goes first into the blood and then some go to the liver..
The case of @cetm-419 proves it. He cant take 10mg oral minoxidil, but sublingually he is taking 12mg right?
Of course it would be great to have good studies.
@bassie21 do you think that theory is logical? You are right that some minoxidil is going to the liver, but may be the amount is so small that cant cause hemodynamic sides, or at least very little

 

[bassie21]

The theory is that sublingual minoxidil cause less hemodynamic effects because it goes first into the blood and then some go to the liver..
The case of @cetm-419 proves it. He cant take 10mg oral minoxidil, but sublingually he is taking 12mg right?
Of course it would be great to have good studies.
@bassie21 do you think that theory is logical? You are right that some minoxidil is going to the liver, but may be the amount is so small that cant cause hemodynamic sides, or at least very little

ok I tried to understand better what happens, orally vs GI. this is what I could find:

"When a chemical comes in contact with the mucous membrane beneath the tongue, it is absorbed. Because the connective tissue beneath the epithelium contains a profusion of capillaries, the substance then diffuses into them and enters the venous circulation.[1] In contrast, substances absorbed in the intestines are subject to first-pass metabolism in the liver before entering the general circulation.

Sublingual administration has certain advantages over oral administration. Being more direct, it is often faster,[quantify] and it ensures that the substance will risk degradation only by salivary enzymes before entering the bloodstream, whereas orally administered drugs must survive passage through the hostile environment of the gastrointestinal tract, which risks degrading them, by either stomach acid or bile, or by enzymes such as monoamine oxidase (MAO). Furthermore, after absorption from the gastrointestinal tract, such drugs must pass to the liver, where they may be extensively altered; this is known as the first pass effect of drug metabolism. Due to the digestive activity of the stomach and intestines, the oral route is unsuitable for certain substances, such as salvinorin A."

so generally speaking, it seems there's a real difference between the two routes after all. whether this applies to minoxidil as well has not been proven yet. furthermore, until there's a double-blind, randomized, placebo-controlled trial on oral minoxidil vs GI all we have is anecdotal evidence so at the moment it's everyone's guess imo.

maybe, just maybe, if you're already taking like 5 mg's per day, one could try taking 2.5 mg sublingually in the morning and 2.5 mg orally in the evening and provide us with some feedback. I'm especially interested in bloodpressure (so, measured, not subjective description etc). I'm not a doctor, so this is not medical advice.

I would also STRONGLY advice against taking more of this drug if taken sublingually because of the hypothesis that this route has less sides. Minoxidil is a potentially dangerous drug so do not experiment with it. Stick with the dosages which have been proven to be safe. I'm not a doctor, but this is my advice anyway.

 

[cetm-419]

The theory is that sublingual minoxidil cause less hemodynamic effects because it goes first into the blood and then some go to the liver..
The case of @cetm-419 proves it. He cant take 10mg oral minoxidil, but sublingually he is taking 12mg right?
Of course it would be great to have good studies.
@bassie21 do you think that theory is logical? You are right that some minoxidil is going to the liver, but may be the amount is so small that cant cause hemodynamic sides, or at least very little

anecdotal evidence like mine, does not bare any scientific methodology, and thus, fails as scientific evidence; which is needed to prove a theory like that from Rodney Sinclair.

and yes, I've been using 12.5 sublingually for the last 3 weeks, I tried 6.25mg for the first weeks. I have not experienced ANY hemodynamic side effect. (tachycardia, hypotension --> dizziness and/or nausea, edema). I check my resting heart rate at various times since drug administration (heart rate is obviously very variable throughout the day, and I only use this parameter to be sure it's in the correct physiological levels). if I were to find any abnormalities, I'd immediately drop the dose back. I plan to drop it at the 6-8 weeks, I'd like to estimate how much sublingual works at least comparing the degree of hypertrichosis, before committing to it for a longer period of time at a low dose.

 

[cetm-419]

ok I tried to understand better what happens, orally vs GI. this is what I could find:

"When a chemical comes in contact with the mucous membrane beneath the tongue, it is absorbed. Because the connective tissue beneath the epithelium contains a profusion of capillaries, the substance then diffuses into them and enters the venous circulation.[1] In contrast, substances absorbed in the intestines are subject to first-pass metabolism in the liver before entering the general circulation.

Sublingual administration has certain advantages over oral administration. Being more direct, it is often faster,[quantify] and it ensures that the substance will risk degradation only by salivary enzymes before entering the bloodstream, whereas orally administered drugs must survive passage through the hostile environment of the gastrointestinal tract, which risks degrading them, by either stomach acid or bile, or by enzymes such as monoamine oxidase (MAO). Furthermore, after absorption from the gastrointestinal tract, such drugs must pass to the liver, where they may be extensively altered; this is known as the first pass effect of drug metabolism. Due to the digestive activity of the stomach and intestines, the oral route is unsuitable for certain substances, such as salvinorin A."

so generally speaking, it seems there's a real difference between the two routes after all. whether this applies to minoxidil as well has not been proven yet. furthermore, until there's a double-blind, randomized, placebo-controlled trial on oral minoxidil vs GI all we have is anecdotal evidence so at the moment it's everyone's guess imo.

maybe, just maybe, if you're already taking like 5 mg's per day, one could try taking 2.5 mg sublingually in the morning and 2.5 mg orally in the evening and provide us with some feedback. I'm especially interested in bloodpressure (so, measured, not subjective description etc). I'm not a doctor, so this is not medical advice.

I would also STRONGLY advice against taking more of this drug if taken sublingually because of the hypothesis that this route has less sides. Minoxidil is a potentially dangerous drug so do not experiment with it. Stick with the dosages which have been proven to be safe. I'm not a doctor, but this is my advice anyway.

I knew you'd be into the topic! it's really interesting.

speaking of sublingual absorption:

minoxidil has a pka of 4.6, and the pka of the floor of the mouth is 6.5. wouldn't this have a negative impact on sublingual absorption? only 1% of the drug would be lipophilic.

at least it's a small molecule (209u), so theoretically speaking, it should diffuse "easily" through the mucous membrane, to reach the blood vessels in the subepithelial connective tissue.

Advances in Nanoparticulate Drug Delivery Approaches for Sublingual and Buccal Administration - PMC

The sublingual and buccal routes of administration have significant advantages for both local and systemic drug delivery. They have shown to be an effective alternative to the traditional oral route, especially when fast onset of action is required. ...

www.ncbi.nlm.nih.gov

"The pH of the saliva can affect drug absorption by affecting the ionization state of drugs. Drug molecules predominantly undergo passive absorption pathways via transcellular diffusion (through the cell) or paracellular diffusion (between cells), depending on their physicochemical characteristics"

"Transcellular diffusion is the most common mechanism and is usually proportional to the lipid solubility of the drug. Therefore, absorption is favored when the drug molecule is in the non-ionized form, which is much more lipophilic than the ionized form. For sublingual and buccal administration, this means that drugs with a high pKa value are preferred due to the relatively neutral pH of the saliva"

BUT --> "Conversely, the paracellular pathway is favored for more hydrophilic or ionized molecules"

- minoxidil will be negatively charged (ionized) when deprotonated in the saliva.

PS: I'll measure my bp before and after dropping my dose to compare.

 

[cetm-419]

I'm sure the topical solution absorbs better sublingually than when applied topically, but to what degree? before thinking of any benefits of sublingual min like minimizing hemodynamic effects, i worry about absorption I think, because maybe proper sublingual compounding of minoxidil has something to help with that pka problem. you know more about these topics, I'd love some insight.

this is theorizing of course.

 

[bassie21]

I'm sure the topical solution absorbs better sublingually than when applied topically, but to what degree? before thinking of any benefits of sublingual min like minimizing hemodynamic effects, i worry about absorption I think, because maybe proper sublingual compounding of minoxidil has something to help with that pka problem. you know more about these topics, I'd love some insight.

this is theorizing of course.

it has already been proven that oral minoxidil is superior to any other hairloss remedy, including topical minoxidil:

besides being more effective, oral minoxidil use also has acceptable/manageable side effects:

so, why not just focus on these facts, rather than hypothesizing/circular reasoning that orally taken minoxidil works better/worse than sublingually and doing potentially dangerous experiments with higher doses bc of some unproven theory? sometimes, just 'good' should be 'good enough' right?

 

[Moz5x]

it has already been proven that oral minoxidil is superior to any other hairloss remedy, including topical minoxidil:

View attachment 165652


besides being more effective, oral minoxidil use also has acceptable/manageable side effects:

View attachment 165653

so, why not just focus on these facts, rather than hypothesizing/circular reasoning that orally taken minoxidil works better/worse than sublingually and doing potentially dangerous experiments with higher doses bc of some unproven theory? sometimes, just 'good' should be 'good enough' right?

From my experience, the lower leg edema from 2.5mg is manageable IF I am careful with my sodium intake. Not always easy to do. The best results however tend to come from 5mg+ but side effects are known to ramp up significantly with increased OM doses. Sublingual interests me because I could potentially minimize the hemodynamic effects (which will likely be much worse for me as I titrate up) and still reap the benefits of the higher dosage.
Aside from that my other main concern is the effects of long term usage. We really need to have proper studies that track low dose OM use >1yr. Given the increasing popularity of low dose OM among hair transplant doctors in Europe and NA in recent years I suspect we will eventually get that data.

 

[Lurker otto]

Thanks for the responses!
And thats my case too, 5mg oral is good but not enough, and i need a much bigger effect for my hair.
Thats why i want to try sublingual too, may be i can reach a better effect, safely of course.

 

[bassie21]

So I've been measuring my BP since I started taking minoxidil orally once day in May (and 2 x 2.5 mg/day from 16/6). It's only one data point, but since I started to take minoxidil sublingually yesterday just for the sake of experiment, my systolic BP went up again (diastolic went down, but only marginally). More datapoints are definitely needed, but based on this one measurement there might be support for the theory that taking minoxidil sublingually indeed decreases BP side effects.

BTW: My BP was too high to start with, so I'm going back to oral ingestion, at least while I'm still @ 5mg/day. Dotted red and green lines are my BP targets.

As always: I'm just a mad scientist, not a doctor at all. This is not medical advise.

 

[LouisSarkozy]

it has already been proven that oral minoxidil is superior to any other hairloss remedy, including topical minoxidil:

View attachment 165652


besides being more effective, oral minoxidil use also has acceptable/manageable side effects:

View attachment 165653

so, why not just focus on these facts, rather than hypothesizing/circular reasoning that orally taken minoxidil works better/worse than sublingually and doing potentially dangerous experiments with higher doses bc of some unproven theory? sometimes, just 'good' should be 'good enough' right?

sorry to ask but according to this study 5mg of oral min beats any dose of topical min theorically? or would applying 10 ml of topical min per day is superior to using 5mg. i'm retarded so sory to ask but i've bee wondering what would work best

 

[Lurker otto]

anecdotal evidence like mine, does not bare any scientific methodology, and thus, fails as scientific evidence; which is needed to prove a theory like that from Rodney Sinclair.

and yes, I've been using 12.5 sublingually for the last 3 weeks, I tried 6.25mg for the first weeks. I have not experienced ANY hemodynamic side effect. (tachycardia, hypotension --> dizziness and/or nausea, edema). I check my resting heart rate at various times since drug administration (heart rate is obviously very variable throughout the day, and I only use this parameter to be sure it's in the correct physiological levels). if I were to find any abnormalities, I'd immediately drop the dose back. I plan to drop it at the 6-8 weeks, I'd like to estimate how much sublingual works at least comparing the degree of hypertrichosis, before committing to it for a longer period of time at a low dose.

You are taking 12,5mg of minoxidil sublingual and 5 mg of oral minoxidil? Or just sublingual?

 

[cetm-419]

So I've been measuring my BP since I started taking minoxidil orally once day in May (and 2 x 2.5 mg/day from 16/6). It's only one data point, but since I started to take minoxidil sublingually yesterday just for the sake of experiment, my systolic BP went up again (diastolic went down, but only marginally). More datapoints are definitely needed, but based on this one measurement there might be support for the theory that taking minoxidil sublingually indeed decreases BP side effects.

BTW: My BP was too high to start with, so I'm going back to oral ingestion, at least while I'm still @ 5mg/day. Dotted red and green lines are my BP targets.

As always: I'm just a mad scientist, not a doctor at all. This is not medical advise.

View attachment 165666

this is great! i

If there is anything relevant soon, in terms if hair or hypertrichosis, I'll update for sure.

 

[cetm-419]

You are taking 12,5mg of minoxidil sublingual and 5 mg of oral minoxidil? Or just sublingual?

yes, both.

in a few weeks I'll lower my sublingual dose btw. (the dizziness I had with oral minoxidil hasn't appeared, this could suggest that minimizing of hemodynamic effects actually works to some extent; although it could also be my body getting used to the medication).

 

[bassie21]

sorry to ask but according to this study 5mg of oral min beats any dose of topical min theorically? or would applying 10 ml of topical min per day is superior to using 5mg. i'm retarded so sory to ask but i've bee wondering what would work best

using 10 ml of a 5% minoxidil topical product means you're putting 500 mg of minoxidil on your scalp in a single application. totally unknown how much of that would get into your bloodstream, but I would never ever take the risk that even 2.5% of that 500 mg would.

 

[LouisSarkozy]

using 10 ml of a 5% minoxidil topical product means you're putting 500 mg of minoxidil on your scalp in a single application. totally unknown how much of that would get into your bloodstream, but I would never ever take the risk that even 2.5% of that 500 mg would.

i've been doing that for 8 years now ( my brother aswell) and it's been the only thing stopping my frontal hairloss and i got no health related sides ( heart or stuff like that) but it just ruins my skin.

though 5 mg of oral min was absolutely superior o any osage of topical as stated by dr donovan with this graph and supposedely according to him even top tier reponder to topical min only gets 21ng/ml in the bloodtream which is inferior to what 2.5 oral min gives in term of systemic absorption

( i don't know how many ml they used tho)


"However, some patients using topical minoxidil occassionally do acheive much higher levels or minoxidil in the blood - even levels up to 21 ng/mL. Fortunately that is uncommon "- See more at: https://donovanmedical.com/hair-blog/oral-minoxidil-top-10#sthash.jT5vM4dj.dpuf


i'm srsly confused what's better now .... thanks

 

[michel sapin]

@bassie21 ; i have been using insane dosage of topical ( because of diffuse thinning) for years and never get hypertrichosis. And after 1.25 mg oral min for 3 month i get huge hypertrichosis. SO i think oral min is way more systemic than any dosage of topical i guess.

 

[vondoom]

@bassie21 ; i have been using insane dosage of topical ( because of diffuse thinning) for years and never get hypertrichosis. And after 1.25 mg oral min for 3 month i get huge hypertrichosis. SO i think oral min is way more systemic than any dosage of topical i guess.

that is how topical works, of course you dont get hypertrichosis from
topical, unless you drink it...

 

[Finasteridegyno]

that is how topical works, of course you dont get hypertrichosis from
topical, unless you drink it...

I got mild all over the body hypertricosis from topical min …..

 

[vondoom]

I got mild all over the body hypertricosis from topical min …..

sounds strange to me... or you needle before application? if not, that is the first time i heard about it (i believe you, though)...

 

[Finasteridegyno]

sounds strange to me... or you needle before application? if not, that is the first time i heard about it (i believe you, though)...

No microneedling. I’ m afraid that oral min will give me the same results of topical