2014年3月4日火曜日

Topical clofibrate (0.25%w/w) is available through Dr. Fukaya’s web shop.



 Topical clofibrate is a non-steroidal ointment but can suppress mild eczema without rebound phenomenon. The anti-inflammatory effect is weaker than topical steroids.  It can be used individually or simultaneously with the Dr Fukaya’s skin repair lotion (hyaluronan lotion of 100,000 dalton ). As the hyaluronan lotion only prevents skin atropy due to steroids or helps to recover from it and doesn’t work as an anti-inflammatory agent, combination therapy of the lotion and topical clofibrate is recommended for better results to eczema-sufferers.

 Topical clofibrate is an ointment easy to be prepared by any physician or pharmacist. The materials needed are clofibrate capsules which is widely available, cheap and old medication for hyperlipidemia and white petrolatum as a base ointment. The base ointment is not limited to white petrolatum. You can mix clofibrate to anything you prefer or whatever your skin can tolerate. Even water can be used as a base (oil in water emulsion).

 The above photo shows aspiration of clofibrate by a medical syringe and needles from the capsule. Clofibrate is oily transparent liquid and the specific gravity is 1.14. One capsule contains 250mg (0.21ml).



 By aspiration from about 7 capsules, one can collect about 1.1ml of clofibrate. It weighs 1.25grams and is just the amount for 0.25%w/w in 500 gram base.

 White petrolatum is a solid material at the room temperature.

  The melting point of white petrolatum is about 38-60℃. So it becomes liquid completely at the temperature of 70℃. One can add the clofibrate to the white petrolatum liquid and mix them to make uniform.

  After cooling, it returns to solid ointment again and the clofibrate ointment (0.25%w/w) is prepared.

 What is the mechanism of clofibrate as an anti-inflammatory agent? How does it work? It is a little complicated. Clofibrate is one of PPAR alpha ligands. PPAR alpha activates NFkappaB which stimulates to produce TSLP in keratinocytes. The below figure shows the vicious cycle in atopic dermatitis which was elucidated by Matsuoka et al in 2012 (J Clin Invest. 2012 Jul 2;122(7):2590-600). The PPAR alpha ligand such as clofibrate works at the point of red arrow and terminates the vicious cycle.
  There is an interesting report about topical PPAR ligands. Hatano et al reported that a kind of topical PPAR alpha ligand, which had been revealed to suppress mild eczema but have not enough power to suppress severe eczema, can suppress experimental rebound phenomenon after continuous topical steroid use in mice. In the experiment, mice were treated to express eczema by some allergen artificially on the skin, followed by topical steroids application and then continued to be applied topical steroids in one group and replaced to topical PPAR alpha ligands in the other group. The former group developed rebound while the latter didn’t (J Invest Dermatol. 2011 Sep;131(9):1845-52).  


The figure is referred from Hatano’s article above mentioned.

 So if topical steroids therapy is changed to topical PPAR alpha ligand therapy on the way the eczema subsides, sufferers are estimated to have less risk to develop rebound phenomenon. Moreover, as topical PPAR alpha ligands themselves have weak anti-inflammatory effect, eczema sufferers may try to use them as the first choice before using steroids.

 The most recommended usage of my hyaluronan lotion and topical clofibrate for prevention of rebound by topical steroids is summarized as the followings.

1 When you apply topical steroids, add my hyaluronan lotion to the area for the purpose of prevention of epidermal atrophy.

2 After the eczema subsided from severe into mild by topical steroids, change them to topical clofibrate.

3 If the eczema is enough mild, topical clofibrate can suppress the eczema without using any topical steroids.

4 For aged eczema sufferers especially over 60 years old at age, the combination therapy of my hyaluronan lotion and topical clofibrate is highly recommended because the aged atrophy of epidermis contributes to the eczema itself more or less.

 I was very much interested in Hatano’s paper and made up my mind to confirm the utility of topical clofibrate by myself two years ago. So I announced my idea through internet in Japanese and collected 20 patients who would participate in my study. They were divided into two groups double-blindly and the effects were compared between the topical clofibrate applied group and placebo group. The efficacy of objective and subjective symptoms was confirmed significantly and TARC in the clofibrate group also decreased significantly while placebo group not. The whole results of the study was made up to an article and published in the Journal of Drugs in Dermatology. 2014 Mar;13(3).


From my experience of 20 patients, I should add some impression about topical clofibrate. They are as follows:

1 There exist topical clofibrate responder and non-responder. It doesn’t correlate with whether the patient is addicted to topical steroids or not.

2 Even in topical clofibrate responders, abrupt aggravation due to exposure to some factor (allergen etc.) can occur. Patients who chose non- steroidal way and expected much in topical clofibrate are liable to be disappointed in case of such aggravation. Patients with steroid-phobia might even misunderstand the aggravation as the rebound to topical clofibrate.

 So I suggest to topical clofibrate users (especially steroid-phobic patients) as the followings:

1 Try topical clofibrate anyway for about two weeks to one month.

2 If you feel effective, continue to apply it instead of your moisturizer. It seems to have no addicted tendency judging from my observation of several topical clofibrate responders for about one year.

3 If the eczema becomes worsened abruptly, don’t be too much depressed. Remember any abrupt aggravation means a hint for you to find out the aggravating factor in your own case. You may use steroids temporarily or may just endure the severe period until recovery. Even if you use topical steroids, you can change them to topical clofibrate after the eczema subsides and avoid topical steroids addiction.

 As I have already mentioned, manufacturing of topical clofibrate is very easy for physicians or pharmacists. However, if you can’t find such cooperative medical professionals, you can purchase it through Dr. Fukaya’s web shop from me. The price is JPN 3,000 at the amount of 500 grams.

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