Hirman Bimatroprost accelerates hair growth by 30% in one study

And it caused hair to grow longer as well. Are you really going to say that this is not impressive???

Here’s another one:

Check out the video in the second link. It appears that Allergan used these people’s results as an aid in figuring out the correct dose of bimatoprost to use for scalp hair growth. These people in the video know the correct dose of bimatoprost to use for scalp hair growth.

Another interesting article about bimatoprost:

And another:

http://www.revoptom.com/content/c/37726/

And here is another story about it:

In this last story note the following statements:

Results from the Phase II clinical trials taking place in the US and Germany should be available before the end of the year.

They involve 220 men with male pattern baldness and 172 women with female pattern baldness.

Participants are undergoing six months treatment either with a solution of bimatoprost, applied to the scalp, or an inactive placebo.

A comparison with the baldness treatment minoxidil is also being assessed.

Prof Randall acts as a consultant to Allergan Inc which manufactures Lumigan.

These statements are important because they indicate the length of time of the completed phase 2 study. The phase 2 study is completed and it was 6 months long. So if Allergan moves onto phase 3 then it might only be a 6 month study. I read time and time again where people say that these studies have to be at least one year long and I tell people that is not necessarily true. The length of time the study has to take is determined on a case-by-case basis.

Here’s the actual phase 2 study and it is clearly completed:

http://clinicaltrials.gov/show/NCT01325337

Note that we are talking about a once daily application here so it will be easier to apply.

Only a fool would get a hair transplant at this point Hairman. You might be able to recover a surprising amount of new hair from bimatoprost soon. Will it give you back all of your hair? No. Will it give you back as much hair as you want? NO. But it could give you enough hair to make hair loss bearable while we wait for Histogen and Aderans. I think you should hang in there and wait for bimatoprost rather than let these HT butchers tear up your scalp. I’m thinking a generic form of high dose bimatoprost should become avail to us by summer or fall at the latest.

i really hope this works… but i used lumigan (bimatoprost) for around three weeks in the past and had to stop it because it made acne popping up on my forehead, thickened my eyebrows n grew small tiny hair on my forehead above eyebrows, area where i dint want hair to grow.

i didnt notice this stupid hairgrowth on my forehead first but it was my friends at the college who brought my attention to it… they didnt know i was using da stuff… one friend pointed dat out on one occasion bt i ignored. but when others told me on different occasions i really got tentative about this stuff.

i had to drop this stuff because all it did was caused small extra hair n acnes (nt da allergic rash, the real acne that you get on face due to androgens) grow down on my forehead, and didnt do anything on the hairline where i actually applied it bt i feel it rather worsened it… Somehow i have this feeling that it aggravates hairloss because what it did with me was what happens when you have elevated androgens. acne, hirsutism(hair growth on unwanted areas) n hairline detrioriation.

my experience with it was bad but i hope it turns out otherwise in trials.

» And it caused hair to grow longer as well. Are you really going to say
» that this is not impressive???
»
» My Hair Growth offers bimatoprost, the latest treatment for scalp hair loss -- My Hair Growth | PRLog
»
» Here’s another one:
»
» Bimatoprost hair loss treatment shows promise -- My Hair Growth | PRLog
»
» Check out the video in the second link. It appears that Allergan used these
» people’s results as an aid in figuring out the correct dose of bimatoprost
» to use for scalp hair growth. These people in the video know the correct
» dose of bimatoprost to use for scalp hair growth.
»
» Another interesting article about bimatoprost:
»
» Common eye drug could lead to baldness treatment | Daily Mail Online
»
» And another:
»
» http://www.revoptom.com/content/c/37726/
»
» And here is another story about it:
»
» http://www.mirror.co.uk/news/technology-science/science/bimatoprost-glaucoma-drug-lumigan-could-1401947
»
» In this last story note the following statements:
»
» Results from the Phase II clinical trials taking place in the US and
» Germany should be available before the end of the year.
»
» They involve 220 men with male pattern baldness and 172 women with female
» pattern baldness.
»
» Participants are undergoing six months treatment either with a solution of
» bimatoprost, applied to the scalp, or an inactive placebo.
»
» A comparison with the baldness treatment minoxidil is also being assessed.
»
» Prof Randall acts as a consultant to Allergan Inc which manufactures
» Lumigan
.
»
»
» These statements are important because they indicate the length of time of
» the completed phase 2 study. The phase 2 study is completed and it was 6
» months long. So if Allergan moves onto phase 3 then it might only be a 6
» month study. I read time and time again where people say that these
» studies have to be at least one year long and I tell people that is not
» necessarily true. The length of time the study has to take is determined
» on a case-by-case basis.
»
»
Thats great, but intresting, if they will work after the hair transplants… cause i’ve already had one…What do u think? and not only bim, but histogen 2. will the work if a person already had a transplant?

» » And it caused hair to grow longer as well. Are you really going to say
» » that this is not impressive???
» »
» »
» My Hair Growth offers bimatoprost, the latest treatment for scalp hair loss -- My Hair Growth | PRLog
» »
» » Here’s another one:
» »
» »
» Bimatoprost hair loss treatment shows promise -- My Hair Growth | PRLog
» »
» » Check out the video in the second link. It appears that Allergan used
» these
» » people’s results as an aid in figuring out the correct dose of
» bimatoprost
» » to use for scalp hair growth. These people in the video know the
» correct
» » dose of bimatoprost to use for scalp hair growth.
» »
» » Another interesting article about bimatoprost:
» »
» »
» Common eye drug could lead to baldness treatment | Daily Mail Online
» »
» » And another:
» »
» » http://www.revoptom.com/content/c/37726/
» »
» » And here is another story about it:
» »
» »
» http://www.mirror.co.uk/news/technology-science/science/bimatoprost-glaucoma-drug-lumigan-could-1401947
» »
» » In this last story note the following statements:
» »
» » Results from the Phase II clinical trials taking place in the US and
» » Germany should be available before the end of the year.
» »
» » They involve 220 men with male pattern baldness and 172 women with
» female
» » pattern baldness.
» »
» » Participants are undergoing six months treatment either with a solution
» of
» » bimatoprost, applied to the scalp, or an inactive placebo.
» »
» » A comparison with the baldness treatment minoxidil is also being
» assessed.
» »
» » Prof Randall acts as a consultant to Allergan Inc which manufactures
» » Lumigan
.
» »
» »
» » These statements are important because they indicate the length of time
» of
» » the completed phase 2 study. The phase 2 study is completed and it was
» 6
» » months long. So if Allergan moves onto phase 3 then it might only be a
» 6
» » month study. I read time and time again where people say that these
» » studies have to be at least one year long and I tell people that is not
» » necessarily true. The length of time the study has to take is
» determined
» » on a case-by-case basis.
» »
» »
» Thats great, but intresting, if they will work after the hair transplants…
» cause i’ve already had one…What do u think? and not only bim, but
» histogen 2. will the work if a person already had a transplant?

I read somewhere that it would work with transplants. The source I got the info from is credible. I think the source I got it from is Zeiring. I think he said it in a Spencer Kobren interview. I also think that Aderans will be available sooner - probably 2014 or 2015 right here in the United States. Histogen will likely be available overseas in 2014 or 2015 but won’t be avail in America until 2017 or 2018. If Histogen wants to compete against Aderans for the pent-up customer demand they will have to release sooner overseas than they plan to or else they will lose the lion’s share of business to Aderans IF ADERANS TREATMENT PROVES TO BE SUCCESSFUL.

Look at it like this: if Aderans is successful and it becomes avail in 2015 why would any Americans fly overseas to another country to get Histogen in the same time frame? They won’t. That is, unless Histogen’s treatment is the better treatment, and Histogen’s treatment is a better treatment. Aderans treatment moved cells from donor hairs to your thinning areas so that means that once the new hairs in the thinning hairs start to grow out those new hairs could take on the characteristics of your donor hairs. Collectively your hair would not look like it did before hair loss started because the hair on the top of your head looks different from the hair on the back of your head, and the hair on the side of your head looks different from the hair on the back of your head. However, you could probably blow dry it and it would all come out looking the same so there is a solution. But Histogen does not transplant cells from one area to another - Histogen works by a different mode of action. So Histogen has the potential to make your hair look exactly like it did before you started losing your hair. Still, since you could probably blow dry it all out it would likely all look fine after the Aderans treatment so Aderans has the advantage over Histogen and the only way Histogen can overcome that advantage that Aderans has is to release it early somewhere in the world and start getting a lot of positive word of mouth. If Histogen doesn’t do this, and if Aderans treatment is successful, then Histogen is the big loser in the GREAT HAIR GROWTH GOLDEN OPPORTUNITY contest. They will lose literally tons of money that they could have gotten instead. The thing is that if Aderans phase 2 studies prove to be successful then that puts Histogen under a lot of pressure and I will go back to the well and “nag” them about releasing their treatment early somewhere. They will almost certainly refuse but if they do then they will definitely lose BIG to Aderans if Aderans treatment is successful. And remember that for Aderans treatment to be successful it does not necessarily have to completely fill in balding areas, rather it just has to somewhat fill in balding areas and ALSO get peach fuzz into the balding areas where it does not induce quality hair to grow because if they can get peach fuzz to grow again then we can use bimatoprost to turn that peach fuzz back into real hair.

If Aderans puts out good evidence in a few months (from their phase 2) then the heat is definitely on Histogen. Histogen intends to release their product in 2015 somewhere overseas and they will want us to fly from our home countries to get it in the country they release it in but why should we do that if Aderans can do a pretty good of giving us our hair back right in our own home countries? The only reason we would go through all the trouble to fly to some other country to get Histogen rather than just getting Aderans is if:

  1. Histogen is the better treatment (which it is)

  2. Histogen will release their product early…a lot earlier.

» 1. Histogen is the better treatment (which it is)
»
» 2. Histogen will release their product early…a lot earlier.
great answer, thank u so much. This year is gonna be a great year! i know that!

» » 1. Histogen is the better treatment (which it is)
» »
» » 2. Histogen will release their product early…a lot earlier.
» great answer, thank u so much. This year is gonna be a great year! i know
» that!

I’m not saying that Histogen will definitely release their product early. I doubt it if they will. But if we get good results from Aderans in the next couple months then if Histogen doesn’t release earlier (somewhere in the world where they can legally release it early) then they will lose so much money it’s staggering. And I am not kidding. People always talk about some event taking place that is staggering and 99.9% of the time they are full of sh!t, but this time I’m right. Look at it like this: If Aderans has good results and it becomes avail in US in 2014 or 2015 would you bother flying to some other country to get Histogen instead? Of course not. Why would you go through all the trouble and expense to get Histogen overseas when you can just stay here and get Aderans instead (assuming Aderans proves to be successful)?

The only chance Histogen (overseas) will have to compete with Aderans (inside the US) is if Histogen’s product is better plus if Histogen will release early than they intend to. They intend to release in 2015. If they wait that long, and if Aderans is a good enough treatment to satisfy bald people, then Histogen will lose B-I-G to Aderans unless Histogen does something bold such as release earlier than their intended 2015 target date somewhere overseas. If Aderans releases great results in the next few months then Histogen needs to release (somewhere in the world) very soon so they can grab the confidence of the bald customer. It would be Histogen’s only chance to compete with Aderans.

I don’t think that Histogen will release it earlier than they plan (2015) but if they don’t it won’t hurt us because we will just stay in our own country and use Aderans instead but it will hurt Histogen in a big BIG way profit wise. There is a lot of pent-up demand and if Histogen won’t release early then Aderans will get all of that pent-up demand purchase. Histogen’s treatment is the better treatment so lots of us balding guys would fly somewhere to get it but if Histogen is going to make us wait longer than Aderans then we will just go Aderans instead. In order for Histogen to compete with Aderans they would have to release 6 months or so before Aderans so that Histogen can build up a reputation for restoring hair to the exact same look as it had before your hair loss started. It takes time to earn that reputation. They have to release in late 2013 or 2014 somewhere in the world if they are to have a chance of competing with Aderans. Aderans does not have to worry about the clock; Histogen does.

» » » 1. Histogen is the better treatment (which it is)
» » »
» » » 2. Histogen will release their product early…a lot earlier.
» » great answer, thank u so much. This year is gonna be a great year! i
» know
» » that!
»
»
»
»

Its definitely a race between the companys, which is good for us… I guess, there will be some updates in the coming months from histogen and aderans… We alreaydy know, that histogen works. At least, its better than everything we have now… So now, they are trying to improve this treatment(higher doses)to show even the better results… And also bimatoprost… Damn, thats great!

» » » » 1. Histogen is the better treatment (which it is)
» » » »
» » » » 2. Histogen will release their product early…a lot earlier.
» » » great answer, thank u so much. This year is gonna be a great year! i
» » know
» » » that!
» »
» »
» »
» »
»
» Its definitely a race between the companys, which is good for us… I guess,
» there will be some updates in the coming months from histogen and
» aderans… We alreaydy know, that histogen works. At least, its better than
» everything we have now… So now, they are trying to improve this
» treatment(higher doses)to show even the better results… And also
» bimatoprost… Damn, thats great!

The race between the companies is very good for us. Aderans has the inside track in terms of timing but Histogen has the best treatment. Still Aderans will put out its’ phase 2 results in the next couple months and if Aderans their results are good enough to make baldness bearable then that will put a lot of pressure on Histogen to do something to get their treatment to market sooner somehow someway or else they will watch from the sidelines as Aderans gets the lion’s share of the business. I’m praying that Aderans results are great for two reasons:

  1. If their results are great then I might just go with Aderans treatment.

  2. If Aderans results are great then that will put Histogen under pressure to release their treatment early somewhere in the world so they can sell it to us and make a profit rather than sit idly by and watch as Aderans gets the business from all of us pent-up balding guys who are ready to pay for a breakthrough treatment right now. The initial wave/surge of customers will produce the kind of profits that will be record setting for any company ever in the history of business. If Histogen doesn’t get in on that then all they will get is some of the newly balding customers after Aderans does all of the pent-up business. And Aderans will get a foothold into the industry so Histogen will have to fight tooth and nail for a share of the new baldies whereas Aderans will have already gotten all of the pent-up business and built itself up a reputation. Aderans will become the industry leader and Histogen will never recover from that.

» » 1. Histogen is the better treatment (which it is)
» »
» » 2. Histogen will release their product early…a lot earlier.
» great answer, thank u so much. This year is gonna be a great year! i know
» that!

I recall reading an interview in which histogen has implied that they in fact will NOT be releasing their product abroad, prior to FDA clearance.

» » » 1. Histogen is the better treatment (which it is)
» » »
» » » 2. Histogen will release their product early…a lot earlier.
» » great answer, thank u so much. This year is gonna be a great year! i
» know
» » that!
»
» I recall reading an interview in which histogen has implied that they in
» fact will NOT be releasing their product abroad, prior to FDA
» clearance.

In fact, that is incorrect. I wouldn’t lie to you Hairman. I know you and I have our ups and downs but I would not lie to you or anyone else. I promise that they are telling me that they will be releasing their product earlier in some countries if that is possible. Even in Zeiring’s recent interview with Kobren Zeiring said it looks like 2015 for Asia and 2017 for America. Zeiring is in tight with Histogen. I posted the interview recently in a different thread and I’ll see if I can find it for you.

http://onlinelibrary.wiley.com/doi/10.1111/exd.12071/full

Abstract

Studies on bimatoprost were performed with two objectives: (i) to determine whether bimatoprost possesses hair growth-stimulating properties beyond eyelash hypertrichosis and (ii) to investigate the biodisposition of bimatoprost in skin for the first time. Bimatoprost, at the dose used clinically for eyelash growth (0.03%) and given once daily for 14 days, increased pelage hair growth in C57/black 6 mice. This occurred as a much earlier onset of new hair growth in shaved mice and the time taken to achieve complete hair regrowth, according to photographic documentation and visual assessment. Bimatoprost biodisposition in the skin was determined at three concentrations: 0.01%, 0.03% and 0.06%. Dose-dependent C max values were obtained (3.41, 6.74, 12.3 μg/g tissue), and cutaneous bimatoprost was well maintained for 24 h following a single dose. Bimatoprost was recovered from the skin only as the intact molecule, with no detectable levels of metabolites. Thus, bimatoprost produces hypertrichosis as the intact molecule.

Background Bimatoprost was originally designed as an ocular hypotensive and has been extensively used for treating glaucoma [1, 2]. Eyelash hypertrichosis was observed as a side effect, and bimatoprost effects on eyelash growth have now been studied in detail [3-5]. Because bimatoprost effects on other hair types have not been reported, we conducted studies on mouse pelage skin [6, 7]. The cutaneous biodisposition of bimatoprost was also investigated because the presence of substantially intact bimatoprost would be indicative of prostamide receptor involvement [8-13].

Questions addressed 1. Do the hypertrichotic properties of bimatoprost extend beyond eyelashes, for example mouse pelage hair [6, 7]? 2. Is bimatoprost metabolically converted in skin? Substantial levels of intact bimatoprost would indicate prostamide receptor mediation [8-13]. Experimental design Pelage hair growth was studied in C57/black 6 mice. The animals were shaved, and hair growth was evaluated by photographic documentation and visual assessment as [1] the time for onset of hair regrowth and [2] the time taken to completely cover the shaved area with new hair. Bimatoprost, at the dose used clinically to treat eyelash hypotrichosis, was given once daily for 14 days. The duration of the experiment was 42 days.

Bimatoprost studies on skin biodisposition were conducted at 0.01%, 0.03% and 0.06% doses. Blood samples were also collected for analysis. Two biodisposition studies were performed, one for 24-h duration and the other for 21-day duration.

Results The effects of once-daily bimatoprost on pelage hair growth are summarised in Fig 1. The time of onset of hair regrowth was essentially halved (Fig. 1a). More importantly, the time taken to cover the shaved back with regrown hair was dramatically and highly significantly reduced (Fig. 1b). Interestingly, bimatoprost appeared to produce a uniform regrowth of hair over the shaved area, rather than radiating out from a central locus as was observed for the control group.

The cutaneous drug levels of graded doses of bimatoprost are depicted in Fig. 2. High concentrations of bimatoprost were rapidly achieved in the skin, and these remained relatively well maintained for 24 hr at about 1 μg/g tissue. In a subchronic 21-day study, no substantial drug accumulation was apparent, but a clear dose–skin concentration relationship was apparent. Supplementary tables provide the C max values, areas under curve and absolute concentrations for both blood and skin. Bimatoprost was found only as the intact molecule in both skin and blood, with no evidence of hydrolytic conversion to 17-phenyl PGF 2α .

Conclusions These studies show, for the first time, the biodisposition of bimatoprost in skin together with its effects on hair growth. The effects of bimatoprost on mouse pelage hair growth were investigated at the same dose as that employed for treating eyelashes [3, 4]. Cutaneous levels of bimatoprost achieved were dose dependent and were well maintained over a 1-day period. Results from a 21-day study provided no evidence for bimatoprost accumulation on repeated dosing with a 0.01% dose, but some accumulation was apparent for the 0.03% and 0.06% doses. Bimatoprost remained as the intact molecule, indicating that it exerts its effects on hair growth by stimulating prostamide receptors [8-13].

Bimatoprost essentially remained as the intact molecule in mouse skin; the putative enzymatic hydrolysis product (17-phenyl PGF 2α ) was only detected twice in a total of 270 separate analyses of different skin and blood samples. Previously, in mouse eyes, it was shown that bimatoprost remains intact [14]. Similarly, PGF 2α -ethanolamide (prostamide F 2α ) remains without significant hydrolytic degradation in mouse blood [15]. On comparing mouse skin and monkey ocular tissue bioavailability [8], it appears that bimatoprost accesses cutaneous tissue more readily and the tissue levels are better maintained than in ocular tissues. These data suggest that once-daily administration to the skin should be adequate to obtain optimal hair growth. This contention presumes that there is a relatively homogeneous distribution of bimatoprost between the hair follicle and the skin layers. A further consideration is that bimatoprost was applied once daily for only 14 days in the hair growth experiment, as an expedient based on limited and overextended manpower resources. It follows that the dosing regimen used in these present studies may have underestimated the effect of bimatoprost on hair growth.

Bimatoprost has long been established as potently effective as the intact molecule, with a pharmacological profile distinct from prostanoid FP receptor agonists and their ester prodrugs [8, 9, 12, 16]. The pharmacology of bimatoprost closely resembles that of prostamide F 2α [9-11]. Further pharmacological characterisation has been achieved by designing selective prostamide antagonists [17-19] and structural elucidation of the prostamide receptor [13]. The results herein indicate hair growth as a further prostamide-mediated effect that may be mimicked by bimatoprost.

Bimatoprost was almost invariably found in blood samples from mice that received topical bimatoprost on shaved skin. Blood levels were about one-thousandth of those present in skin. Although bimatoprost was detected in pharmacologically active levels in mouse blood, this would be greatly ‘diluted’ in the blood by humans as they are about 5000 times heavier/larger. The human scalp area of coverage would be about 10–50 times greater than that of the shaved mouse skin. Presuming similar penetration characteristics for bimatoprost in mouse and human skin, the likely blood concentration in humans would be in the range of 50 pg/ml. Anticipated human blood levels of 10–100 pg/ml are beneath the pharmacologically active levels for bimatoprost [20].

In summary, bimatoprost stimulates the growth of mouse pelage hair. Bimatoprost was found as the intact molecule in mouse skin and blood, indicating that it stimulates hair growth by interacting with prostamide-sensitive receptors [8-13]. These studies indicate that the ability of bimatoprost to stimulate hair growth may extend beyond eyelashes, but effects on human scalp hair growth, for example, cannot necessarily be predicted from mouse pelage hair experiments. The human hair follicle expresses the prostanoid FP receptor [21], but expression of altFP4 [13] is required to predict a positive outcome with bimatoprost.

Thanks for posting this but just for the record I do not know if the dose used in this study is the same dose as the high dose used in the Allergan trials. It might be but I am not sure. If you look at the video in this link:

you will see them showing a square piece of plastic with lots of little pockets in it and what they did was put hair follicles into the pockets and then put different doses of bimatoprost into the pockets with the hair follicles. Then they measured which doses of bimatoprost produced the best hair growth rates. A person (I think a lady) is talking about this while the camera is showing the square piece of plastic with the pockets and she is saying that this is how the correct dose of bimatoprost was determined. The study you are sharing does not talk about the researchers putting hair follicles and bimatoprost into the same square piece of plastic so I do not think that the study you have found gives us the correct high dose. What do you think?

» http://onlinelibrary.wiley.com/doi/10.1111/exd.12071/full
»
» Abstract
»
» Studies on bimatoprost were performed with two objectives: (i) to determine
» whether bimatoprost possesses hair growth-stimulating properties beyond
» eyelash hypertrichosis and (ii) to investigate the biodisposition of
» bimatoprost in skin for the first time. Bimatoprost, at the dose used
» clinically for eyelash growth (0.03%) and given once daily for 14 days,
» increased pelage hair growth in C57/black 6 mice. This occurred as a much
» earlier onset of new hair growth in shaved mice and the time taken to
» achieve complete hair regrowth, according to photographic documentation and
» visual assessment. Bimatoprost biodisposition in the skin was determined at
» three concentrations: 0.01%, 0.03% and 0.06%. Dose-dependent C max values
» were obtained (3.41, 6.74, 12.3 μg/g tissue), and cutaneous
» bimatoprost was well maintained for 24 h following a single dose.
» Bimatoprost was recovered from the skin only as the intact molecule, with
» no detectable levels of metabolites. Thus, bimatoprost produces
» hypertrichosis as the intact molecule.
»
» Background Bimatoprost was originally designed as an ocular hypotensive and
» has been extensively used for treating glaucoma [1, 2]. Eyelash
» hypertrichosis was observed as a side effect, and bimatoprost effects on
» eyelash growth have now been studied in detail [3-5]. Because bimatoprost
» effects on other hair types have not been reported, we conducted studies on
» mouse pelage skin [6, 7]. The cutaneous biodisposition of bimatoprost was
» also investigated because the presence of substantially intact bimatoprost
» would be indicative of prostamide receptor involvement [8-13].
»
» Questions addressed 1. Do the hypertrichotic properties of bimatoprost
» extend beyond eyelashes, for example mouse pelage hair [6, 7]? 2. Is
» bimatoprost metabolically converted in skin? Substantial levels of intact
» bimatoprost would indicate prostamide receptor mediation [8-13].
» Experimental design Pelage hair growth was studied in C57/black 6 mice. The
» animals were shaved, and hair growth was evaluated by photographic
» documentation and visual assessment as [1] the time for onset of hair
» regrowth and [2] the time taken to completely cover the shaved area with
» new hair. Bimatoprost, at the dose used clinically to treat eyelash
» hypotrichosis, was given once daily for 14 days. The duration of the
» experiment was 42 days.
»
» Bimatoprost studies on skin biodisposition were conducted at 0.01%, 0.03%
» and 0.06% doses. Blood samples were also collected for analysis. Two
» biodisposition studies were performed, one for 24-h duration and the other
» for 21-day duration.
»
» Results The effects of once-daily bimatoprost on pelage hair growth are
» summarised in Fig 1. The time of onset of hair regrowth was essentially
» halved (Fig. 1a). More importantly, the time taken to cover the shaved back
» with regrown hair was dramatically and highly significantly reduced (Fig.
» 1b). Interestingly, bimatoprost appeared to produce a uniform regrowth of
» hair over the shaved area, rather than radiating out from a central locus
» as was observed for the control group.
»
» The cutaneous drug levels of graded doses of bimatoprost are depicted in
» Fig. 2. High concentrations of bimatoprost were rapidly achieved in the
» skin, and these remained relatively well maintained for 24 hr at about 1
» μg/g tissue. In a subchronic 21-day study, no substantial drug
» accumulation was apparent, but a clear dose–skin concentration relationship
» was apparent. Supplementary tables provide the C max values, areas under
» curve and absolute concentrations for both blood and skin. Bimatoprost was
» found only as the intact molecule in both skin and blood, with no evidence
» of hydrolytic conversion to 17-phenyl PGF 2α .
»
» Conclusions These studies show, for the first time, the biodisposition of
» bimatoprost in skin together with its effects on hair growth. The effects
» of bimatoprost on mouse pelage hair growth were investigated at the same
» dose as that employed for treating eyelashes [3, 4]. Cutaneous levels of
» bimatoprost achieved were dose dependent and were well maintained over a
» 1-day period. Results from a 21-day study provided no evidence for
» bimatoprost accumulation on repeated dosing with a 0.01% dose, but some
» accumulation was apparent for the 0.03% and 0.06% doses. Bimatoprost
» remained as the intact molecule, indicating that it exerts its effects on
» hair growth by stimulating prostamide receptors [8-13].
»
» Bimatoprost essentially remained as the intact molecule in mouse skin; the
» putative enzymatic hydrolysis product (17-phenyl PGF 2α ) was only
» detected twice in a total of 270 separate analyses of different skin and
» blood samples. Previously, in mouse eyes, it was shown that bimatoprost
» remains intact [14]. Similarly, PGF 2α -ethanolamide (prostamide F
» 2α ) remains without significant hydrolytic degradation in mouse blood
» [15]. On comparing mouse skin and monkey ocular tissue bioavailability [8],
» it appears that bimatoprost accesses cutaneous tissue more readily and the
» tissue levels are better maintained than in ocular tissues. These data
» suggest that once-daily administration to the skin should be adequate to
» obtain optimal hair growth. This contention presumes that there is a
» relatively homogeneous distribution of bimatoprost between the hair
» follicle and the skin layers. A further consideration is that bimatoprost
» was applied once daily for only 14 days in the hair growth experiment, as
» an expedient based on limited and overextended manpower resources. It
» follows that the dosing regimen used in these present studies may have
» underestimated the effect of bimatoprost on hair growth.
»
» Bimatoprost has long been established as potently effective as the intact
» molecule, with a pharmacological profile distinct from prostanoid FP
» receptor agonists and their ester prodrugs [8, 9, 12, 16]. The pharmacology
» of bimatoprost closely resembles that of prostamide F 2α [9-11].
» Further pharmacological characterisation has been achieved by designing
» selective prostamide antagonists [17-19] and structural elucidation of the
» prostamide receptor [13]. The results herein indicate hair growth as a
» further prostamide-mediated effect that may be mimicked by bimatoprost.
»
» Bimatoprost was almost invariably found in blood samples from mice that
» received topical bimatoprost on shaved skin. Blood levels were about
» one-thousandth of those present in skin. Although bimatoprost was detected
» in pharmacologically active levels in mouse blood, this would be greatly
» ‘diluted’ in the blood by humans as they are about 5000 times
» heavier/larger. The human scalp area of coverage would be about 10–50 times
» greater than that of the shaved mouse skin. Presuming similar penetration
» characteristics for bimatoprost in mouse and human skin, the likely blood
» concentration in humans would be in the range of 50 pg/ml. Anticipated
» human blood levels of 10–100 pg/ml are beneath the pharmacologically active
» levels for bimatoprost [20].
»
» In summary, bimatoprost stimulates the growth of mouse pelage hair.
» Bimatoprost was found as the intact molecule in mouse skin and blood,
» indicating that it stimulates hair growth by interacting with
» prostamide-sensitive receptors [8-13]. These studies indicate that the
» ability of bimatoprost to stimulate hair growth may extend beyond
» eyelashes, but effects on human scalp hair growth, for example, cannot
» necessarily be predicted from mouse pelage hair experiments. The human hair
» follicle expresses the prostanoid FP receptor [21], but expression of
» altFP4 [13] is required to predict a positive outcome with bimatoprost.