New Study: Topical Cetirizine For Androgenetic Alopecia Shows Promise

[jgray201]

The Rossi study did not explain how they mixed their solution or the composition in specific. Again this is all avoidable by using an alcohol stable antihistamine.

I completely accept that the study does not provide detail on that and thus it is difficult to know exactly how the solution was prepared and what ways, if any, they negated risks of cetirizine degrading in the solution.

But, studies seem to indicate that Cetirizine's effect on PGD2 and PGE2 and other inflammatory mediators is quite unique. Do other antihistamines have the exact same beneficial effects? If not, isnt that also a gamble?

 

[fuDHTck]

Has someone already tried to contact Rossi and ask about the details?

I could do it in theory since she is also Italian.

 

[sunchyme1]

But, studies seem to indicate that Cetirizine's effect on PGD2 and PGE2 and other inflammatory mediators is quite unique. Do other antihistamines have the exact same beneficial effects? If not, isnt that also a gamble?

@IdealForehead

i would like to know this too if you have the answer mate.

i would prefer to just use deso to avoid the degrading issue but how identical is deso compared to ceti. is it just as effective?

 

[Ollie]

@IdealForehead

i would like to know this too if you have the answer mate.

i would prefer to just use deso to avoid the degrading issue but how identical is deso compared to ceti. is it just as effective?

I think the degrading issue is only an issue if its being stored. If you make weekly batches then it'll obviously be a problem

 

[sunchyme1]

I think the degrading issue is only an issue if its being stored. If you make weekly batches then it'll obviously be a problem

im talking about the uniqueness of ceti not the degrading issue

i would prefer to use deso so i dont have to make it too often, but i just wana know if deso is as effective as ceti, as pointed out by the other guy

i know i should go and read some studies but i am simply too stupid

 

[IdealForehead]

@IdealForehead

i would like to know this too if you have the answer mate.

i would prefer to just use deso to avoid the degrading issue but how identical is deso compared to ceti. is it just as effective?

I don't have any particular answers except that both of these are the same class of medications with the same basic action.

People almost hilariously tend to read into isolated chemical studies that have little meaning. We have to. We don't have that much information available to us. Without a head-head cet-desloratadine hair study one can only guess.

But both of these are 2nd generation antihistamines. The principle of antihistamines for hair is that histamines are presumed to be part of the inflammatory cascade, and once histamines bind to histamine receptors, for example, in mast cells in the scalp, these mast cells release a whole toxic load of inflammatory mediators which worsen male pattern baldness (including PGD2).

Blocking the histamines blocks the inflammation and hair is preserved.

I am not aware of nor could I imagine any situation where cetirizine would do anything all that different from desloratadine (or vice versa). They will have different half lives, and different strengths based on their receptor affinity. But in over the counter treatment of allergies they are basically equivalent, suggesting they do pretty much the same thing.

Many people on the German forum have reportedly tried cetirizine and failed. This could easily be attributed to the alcohol effect.

1) They use it with alcohol, and the cetirizine degrades to a major extent, leading to minimal active ingredient being applied
2) They use it without alcohol, and it does not sufficiently penetrate the scalp to work.

Again, I see no reason to annoy myself with these problems or obsess over it. I researched it, decided on desloratadine, and that's my final decision. I have no interest in mixing multiple different solutions every day and applying multiple mixtures to my head. I have no interest in a compound which isn't stable.

Can I guarantee they will have identical effects? No I can't. But I can guarantee if your cetirizine degrades in alcohol, it almost certainly will do nothing when you apply it to your scalp.

 

[Ollie]

I think the German forum tried Cetirizine and water - perhaps that why it didnt work. The Cetirizine study just used alcohol im fairly sure.

https://www.ncbi.nlm.nih.gov/pubmed/28604133

 

[jgray201]

Has someone already tried to contact Rossi and ask about the details?

I could do it in theory since she is also Italian.

Rossi also used a topical cetirizine solution with Vit D in another study to generate hair growth (for a different disease). I wondered if there was more information in this study about how the solution was prepared. Can't find any information beyond the abstract though.

it would be great if you could try to contact Rossi. I think someone may have tried to earlier on but I'm not sure.

 

[jgray201]

I don't have any particular answers except that both of these are the same class of medications with the same basic action.

People almost hilariously tend to read into isolated chemical studies that have little meaning. We have to. We don't have that much information available to us. Without a head-head cet-desloratadine hair study one can only guess.

But both of these are 2nd generation antihistamines. The principle of antihistamines for hair is that histamines are presumed to be part of the inflammatory cascade, and once histamines bind to histamine receptors, for example, in mast cells in the scalp, these mast cells release a whole toxic load of inflammatory mediators which worsen male pattern baldness (including PGD2).

Blocking the histamines blocks the inflammation and hair is preserved.

I am not aware of nor could I imagine any situation where cetirizine would do anything all that different from desloratadine (or vice versa). They will have different half lives, and different strengths based on their receptor affinity. But in over the counter treatment of allergies they are basically equivalent, suggesting they do pretty much the same thing.

Many people on the German forum have reportedly tried cetirizine and failed. This could easily be attributed to the alcohol effect.

1) They use it with alcohol, and the cetirizine degrades to a major extent, leading to minimal active ingredient being applied
2) They use it without alcohol, and it does not sufficiently penetrate the scalp to work.

Again, I see no reason to annoy myself with these problems or obsess over it. I researched it, decided on desloratadine, and that's my final decision. I have no interest in mixing multiple different solutions every day and applying multiple mixtures to my head. I have no interest in a compound which isn't stable.

Can I guarantee they will have identical effects? No I can't. But I can guarantee if your cetirizine degrades in alcohol, it almost certainly will do nothing when you apply it to your scalp.

Fair enough. The main reason I ask is that I thought Cetirizine's anti-inflammatory mechanism is actually not related to histamine release. That's why I wonder if other drugs of the same class have the exact same effect.

 

[jgray201]

From the Rossi study:
Charlesworth EN et al. showed that cetirizine causes a significant reduction in both the inflammatory cell infiltrate and PGD2 production.
However, these effects apparently are not related to its anti-H1 activity

 

[bassa]

Objective: To determine if the anti-leukotriene zafirlukast is effective in the treatment of acne vulgaris/acne rosacea.

Design: Inception cohort investigational study conducted from October 1999 to January 2000.

Setting: Rural Family Practice clinic in Waldheim, La.

Participants: A total of 7 male and 8 female patients aged 12-45 years diagnosed with mild, moderate, or severe acne vulgaris including one case of acne conglobata and 2 cases of acne rosacea were given 20 mg. of zafirlukast (ACCOLATE® brand from AstraZeneca) twice daily from week 1 through week 4. The dose was increased to 30 mg. twice daily at week 4 and continued through week 8. At week 8 the dose of zafirlukast was decreased to 20 mg twice daily and continued until the termination of the study at 10 weeks.

Between the months of October and November 1999 both adolescent and adult patients were recruited consecutively at a family practice clinic in rural Louisiana to participate in an investigational study to determine the effectiveness of zafirlukast in the treatment of acne vulgarism Those patients who provided informed consent and who have reported a prior medical diagnosis of acne vulgaris were enlisted into the study. This cohort was composed of a total of seven male and eight female Caucasian patients, age twelve to forty five years, diagnosed with mild, moderate or severe acne vulgaris.

Pre-study recruitment assessment data was consistent with the following: one of fifteen patients was diagnosed with acne conglobata; two of fifteen patients were diffused with acne rosacea, one of which had acne scars who had previously been treated with oral isotretinoin for nodular-cystic acne; eleven of fifteen patients with moderate to severe inflammatory/nodular-cystic acne; all patients had self medicated with topical comedolytic over-the-counter agents; three of fifteen patients had never been treated with prescription (topical or systemic) medications; twelve of fifteen patients were prescribed a range of three to five medical prescriptions (both topical and systemic) with varying degrees of success and failure; three of fifteen patients had previously taken oral isotretinoin; two of fifteen patients had been offered oral isotretinoin but refused that treatment.

Inclusion criteria for study enlistment encompassed any patient who was requesting medical treatment of a chief complaint of acne dermatitis, coincident with a clinical diagnosis of acne vulgaris confirmed by physical examination. These patients voluntarily agreed to be treated with zafirlukast knowing that alternative treatment (both topical and systemic) were available. At the initial visit all patients were instructed on the use of zafirlukast This was to be administered by mouth twice daily. The potential side effects, potential adverse reactions, and other risks were all explained. Patients all agreed to avoid any over-the-counter acne preparations and were to use any household soft-soap product to wash the facial skin twice daily. Zafirlukast was to be administered at the dose of 20 mg. twice daily from week one through week four and then to be increased to 30 mg. twice daily at week four and continued through week eight. At week eight the dose of zafirlukast was to be decreased to 20 mg. taken twice daily and continued until the completion of the study at ten weeks.

Main Outcome Measures: Subjective and objective medical examination and qualitative photographic analysis were employed at each patients initial visit to establish baseline. Thereafter, each patient was consecutively examined and photographed at two to three week intervals. At each respective visit, treatment benefits were assessed, compliance was questioned, and side effects, if any, noted. Patient satisfaction was measured by having all participants complete a post study survey. This questionnaire allowed patients to document adversities or side effects, self-esteem improvement, diminution of facial pain and discomfort, and overall satisfaction with the course of treatment. Data was utilized from primary care visits at the Waldheim Family Practice Clinic.

Results: All fifteen patients finished the study and completed the post study survey. Significantly, all participants attained periods of acne remission during the study. Subjective and objective clinical improvement was observed as early as two weeks, but routinely occurred within 3-4 weeks of initiating zafirlukast therapy. All cases of mild, moderate, or severe acne vulgaris studied including acne rosacea, acne conglobata, and nodulocystic acne responded similarly in their observed periods of remissions or exacerbations. The data were correlated with qualitative photographic analysis. Satisfaction ratings in the post study survey were high and most patients preferred to continue zafirlukast alone or as combination therapy with other comedolytic or anti-infective agents.

In so much as there was a continual decline in both inflammatory and non-inflammatory acne lesions during this study, patient self-esteem progressed and appeared to improve by week four, and matured by week eight, only falling off slightly during periods of acne recurrence. Remission of acne vulgaris, characterized by the absence of new lesion formation, old lesion regression and the observed decline in perilesional erythema and facial discomfort, were all factors contributing to the amelioration of patient self-esteem.

Only one patient was compliant in taking zafirlukast throughout the entire study. He was able to maintain complete remission and accomplish total regression of any inflammatory acne lesion. He experienced only a mild facial erythema for two days following the dosage drop from 30 mg to 20 mg.

However, it was not uncommon for patients to miss anywhere from two to three consecutive doses in any one week and six patients had significant dosage discontinuation each at nine, seven, six, five, and two at three consecutive days, respectively. One patient who missed three consecutive days also missed every weekend throughout the entire study. Only one person requested referral to dermatology at the termination of the study. Data analysis revealed that he was one of two participants consistently non-compliant throughout the entire study. It should be noted, however, that medical noncompliance is not a quite uncommon finding during the management of a chronic medical condition during any study and does not reflect the success of the treatment. For example, in this study, factors that contributed to non-compliance include the twice daily dosing requirements, a false sense of well being once remission was realized, the mere fact that most patients whom were non compliant were in the study group compromising those in the teenage years and usually took weekend a retreat from their homes and the guidance of their parents whom were directing their therapy to some degree. There were also those who were content with the remission of new lesions and less inclined to be concerned with the regression of old acne lesions.

Those who were consistently non-compliant had acne reoccurrence within 2-3 days after more than 2-3 doses missed. Discontinuation of zafirlukast therapy over a 5-7 day period was associated with reoccurrence of acne form lesions equal to baseline levels. However, reinstitution of zafirlukast therapy was associated with old lesion regression and new lesion remission, commonly occurring within a period of time resembling the duration of zafirlukast deprivation. There appeared to be no added benefit observed in taking 30 mg. twice daily from week 4 thru week 8.

Although perilesional erythema appeared to resolve only by approximately 10-15% by week two, significant reductions of 40-50% and 80-90% were achieved by weeks four and eight respectively. Remarkably, there was little if any perilesional erythema accompanying the development of any new inflammatory acne lesion that developed while any patient was taking zafirlukast.

One participant who suffered with acne rosacea felt a sense of asthenia in taking zafirlukast on an empty stomach, thereafter she continued the study from week two through, week ten at 10 mg. dosage levels twice daily with no further side effects observed. She was the only participant whom ever realized any potential side effects while being treated with zafirlukast.

Conclusion: This study substantiates efficacy in modifying the inflammatory reaction of acne vulgaris Zafirlukast exerts a potent therapeutic effect on the acne process and plays a pivotal role in the prophylactic management of acne vulgaris. The recommended dosage of zafirlukast for adults (≧12 years) is 20 mg twice daily; for pediatrics (7-11 years) the recommended dosage is 10 mg twice daily. The preferred daily dosage range of zafirlukast for adults (>12 years) is about 20 mg twice daily; for pediatrics (7-11 years) the recommended dosage is about 10 mg twice daily. It is preferably taken twice daily or administered in a form that it is released into the bloodstream twice daily. It is preferably taken consistently for at least 4 weeks, more preferably at least 8 weeks, and even more preferably at least 12 weeks. Most preferably, it is taken every day without stopping. The method of the present invention is most effective if zafirlukast is taken as prescribed every day. Additional controlled studies, such as double blind placebo studies, increasing drug dosage at the onset and throughout entire length of study, prolonged study periods and study protocols that would include anti-leukotriene therapy side by side with comedolytic anti-infective, anti-histamine and anti-androgen therapies will demonstrate the significant value of zafirlukast in patients who suffer from this dreadful disease.

Other Effective Treatments Encompassed by the Present Invention
In addition to zafirlukast, the following drugs will also be effective in treating acne and other inflammatory skin diseases.

Montelukast (such as Singulair®) is another leukotriene blocker. Singulair was tested and shown to be effective. It is a selective and orally active leukotriene receptor antagonist that inhibits the cysteinyl leukotriene receptor. The recommended dosage for adults (≧15 years) is 10 mg in the evening; for pediatrics (6-14 years) the recommended dosage is 5 mg in the evening.

Leukotriene inhibitors (such as cromolyn sodium) will also work, but may be less desirable as they may have harmful side effects. Cromolyn sodium acts by inhibiting the release of histamine and leukotrienes from the mast cell. In vitro and in vivo animal studies show that cromolyn sodium inhibits synthesized mast cell degranulation that occurs after exposure to specific antigens. Cromolyn sodium acts by inhibiting the release of mediators from mast cells. Studies show that cromolyn sodium directly blocks calcium ions from entering the mast cell thereby preventing mediator release. Cromolyn sodium inhibits both the immediate and non-immediate bronchoconstrictor reactions to inhaled antigens. Cromolyn sodiun also attenuates bronchospasm caused by exercise, aspirin, cold air, sulfur dioxide and environmental pollutants (see Physicians' Desk Reference page 987, 50th edition 1966).

Examples of commercially available cromolyn sodium are Gastrocrom®, Intal inhaler®, Intal nebulizer solution, Opticrom Ophthalmic solution and cromolyn sodium inhalation solution USP. The recommended dosage of Gastrocrom® for adults (13+) is two 100 mg ampoules taken orally 4 times per day (800 mg daily total), ½ hour before meals and at bedtime, and for children 2-12, one 100 mg ampoule taken orally 4 times per day (400 mg daily total), ½ hour before meals and at bedtime.

Zileuton (such as Zyflo®) is an oral active inhibitor of 5-lipoxygenase, the enzyme that catalyzes the formation of leukotriene from arachidonic acid. The recommended dosage for adults (≧18 years) is 600 mg four times per day (2400 mg daily total).

Histamines play some role in acne formation, and antihistamines administered daily will help reduce acne formation. Preferred antihistamines include loratadine (e.g. Claritin®), ranitidine (e.g. Zantac®), cimetidine (e.g. Tagamet®), famotidine (e.g. Pepsid®), nizatidine (e.g. Axid®), and fexofenadine (e.g. Allegra®), hydroxyzine HCl (e.g. Atarax), cyprohepadine (e.g Periactin), promethazine HCl (e.g. Phenegan), cetrizine (e.g. Zyrtec), and hydroxyzine pamoate (e.g. Vistaril) because they do not sedate. However, other antihistamines would work as well. It is believed that antihistamines administered daily may help reduce acne formation if taken for 2 months or longer.

Loratadine is especially preferred due to its dual action of acting as an antihistamine and as a leukotriene C4 antagonist

 

[sunchyme1]

From the Rossi study:
Charlesworth EN et al. showed that cetirizine causes a significant reduction in both the inflammatory cell infiltrate and PGD2 production.
However, these effects apparently are not related to its anti-H1 activity

Fair enough. The main reason I ask is that I thought Cetirizine's anti-inflammatory mechanism is actually not related to histamine release. That's why I wonder if other drugs of the same class have the exact same effect.

i think this guy is talking about the same thing. he posted it on another forum

http://www.hairlosshelp.com/forums/messageview.cfm?catid=10&threadid=118811&enterthread=y

 

[jgray201]

i think this guy is talking about the same thing. he posted it on another forum

http://www.hairlosshelp.com/forums/messageview.cfm?catid=10&threadid=118811&enterthread=y

Yeah i think he is. Its an interesting post actually. Although not convinced that histamine itself has a primary role in hair loss/growth.

 

[jgray201]

For anyone interested i think this is similar to what they used in the vehicle. It is supposed to help deliver products to skin and is not greasy. Downside is it does not mix with water, which is why the vehicle in the study is just ethanol.
https://www.amazon.co.uk/Mystic-Mom...etailBullets_secondary_view_div_1525936204315

 

[hopeforhappiness]

For anyone interested i think this is similar to what they used in the vehicle. It is supposed to help deliver products to skin and is not greasy. Downside is it does not mix with water, which is why the vehicle in the study is just ethanol.
https://www.amazon.co.uk/Mystic-Mom...etailBullets_secondary_view_div_1525936204315

Where can I find some more info on using this for delivery ?

 

[INT]

For anyone interested i think this is similar to what they used in the vehicle. It is supposed to help deliver products to skin and is not greasy. Downside is it does not mix with water, which is why the vehicle in the study is just ethanol.
https://www.amazon.co.uk/Mystic-Mom...etailBullets_secondary_view_div_1525936204315

It's a silicone which means not soluble in water. Not a good idea.

 

[jgray201]

It's a silicone which means not soluble in water. Not a good idea.

I dont think there was any water in the study vehicle. It does mix with ethanol however.

 

[Spice_Lord]

I have some what intermediate experience working with drug formulations as a pharmacist in the U.S.

After seeing many here have some what mixed success with topical cetirizine. I would like to point out why it is most likely having no effect (assuming that it does have activity on PGD2). Cetirizine is a zwitterion, meaning it has both a acidic group, and a basic group. This is important because these groups will become charged depending on the pH relative to the pKa of the molecule.

For Cetirizine it looks like the pKa of the basic group is 7.7 and the pKa of the acidic group is 3.6. This means that at a pH of about 7 or below, which is mostly the pH in a formulation dissolved in water, BOTH the basic and acidic group is charged.

Why is being charged bad? The skin is a lipophilic substance, and like attracts like, meaning that it will not readily absorb a charged molecule. Basically, you are wasting drug applying cetirizine dissolved in water on your head.

How do we bypass this? My theory revolves around making a nanoemulsion. Essentially suspending nano-sized droplets of water containing cetirizine in olive oil. The oil will usher the cetirizine to the follicle and disrupt the surface, essentially allowing the cetirizine to sneak in past the defense of the skin.

All you need for this is cetirizine, olive oil, and a surfactant (to form the nano droplets). I will be conducting trials on myself using this preparation. I also plan on adding d-limonene to the water phase to hopefully help with additional penetration.

I am just following the directions detailed in this study, except substituting out the drug they used for cetirizine.


Crocin loaded nano-emulsions: Factors affecting emulsion properties in spontaneous emulsification

I will let you guys know how it goes, currently I am waiting on some glassware to get here from eBay, and then I will begin.

I dont think there was any water in the study vehicle. It does mix with ethanol however.

 

[Ollie]

I have some what intermediate experience working with drug formulations as a pharmacist in the U.S.

After seeing many here have some what mixed success with topical cetirizine. I would like to point out why it is most likely having no effect (assuming that it does have activity on PGD2). Cetirizine is a zwitterion, meaning it has both a acidic group, and a basic group. This is important because these groups will become charged depending on the pH relative to the pKa of the molecule.

For Cetirizine it looks like the pKa of the basic group is 7.7 and the pKa of the acidic group is 3.6. This means that at a pH of about 7 or below, which is mostly the pH in a formulation dissolved in water, BOTH the basic and acidic group is charged.

Why is being charged bad? The skin is a lipophilic substance, and like attracts like, meaning that it will not readily absorb a charged molecule. Basically, you are wasting drug applying cetirizine dissolved in water on your head.

How do we bypass this? My theory revolves around making a nanoemulsion. Essentially suspending nano-sized droplets of water containing cetirizine in olive oil. The oil will usher the cetirizine to the follicle and disrupt the surface, essentially allowing the cetirizine to sneak in past the defense of the skin.

All you need for this is cetirizine, olive oil, and a surfactant (to form the nano droplets). I will be conducting trials on myself using this preparation. I also plan on adding d-limonene to the water phase to hopefully help with additional penetration.

I am just following the directions detailed in this study, except substituting out the drug they used for cetirizine.


Crocin loaded nano-emulsions: Factors affecting emulsion properties in spontaneous emulsification

I will let you guys know how it goes, currently I am waiting on some glassware to get here from eBay, and then I will begin.

Whilst you've said water is an inappropriate vehicle, is alcohol as used in the study fine ? I've heard some say alcohol degrades the Cetirizine, however if you're making daily batches does this remain a problem ?

 

[sunchyme1]

I have some what intermediate experience working with drug formulations as a pharmacist in the U.S.

After seeing many here have some what mixed success with topical cetirizine. I would like to point out why it is most likely having no effect (assuming that it does have activity on PGD2). Cetirizine is a zwitterion, meaning it has both a acidic group, and a basic group. This is important because these groups will become charged depending on the pH relative to the pKa of the molecule.

For Cetirizine it looks like the pKa of the basic group is 7.7 and the pKa of the acidic group is 3.6. This means that at a pH of about 7 or below, which is mostly the pH in a formulation dissolved in water, BOTH the basic and acidic group is charged.

Why is being charged bad? The skin is a lipophilic substance, and like attracts like, meaning that it will not readily absorb a charged molecule. Basically, you are wasting drug applying cetirizine dissolved in water on your head.

How do we bypass this? My theory revolves around making a nanoemulsion. Essentially suspending nano-sized droplets of water containing cetirizine in olive oil. The oil will usher the cetirizine to the follicle and disrupt the surface, essentially allowing the cetirizine to sneak in past the defense of the skin.

All you need for this is cetirizine, olive oil, and a surfactant (to form the nano droplets). I will be conducting trials on myself using this preparation. I also plan on adding d-limonene to the water phase to hopefully help with additional penetration.

I am just following the directions detailed in this study, except substituting out the drug they used for cetirizine.


Crocin loaded nano-emulsions: Factors affecting emulsion properties in spontaneous emulsification

I will let you guys know how it goes, currently I am waiting on some glassware to get here from eBay, and then I will begin.

please keep us updated

you going to be using finasteride along side this?