FLURIDIL

A NOVEL DERMO-COSMETIC AGENT FOR TOPICAL APPLICATION IN ANDROGENIC HAIR LOSS, i.e. EFFLUVIUM AND ALOPECIA

The relationship between the sex hormones and the scalp hair is not yet fully understood. Early in life, estrogens in women and androgens in males make scalp hair grow. Then, usually after 30, for reasons not yet explained, in genetically predisposed males the androgens start pushing the hair out of the follicles, thus causing hair loss. A similar phenomenon occurs in women who have reached a stage in their life when they also produce substantial levels of androgens. Hair loss, which dermatologists call effluvium, ultimately results in alopecia. There are also other reasons for alopecia which dermatologists diagnose and often can treat, but by far the most prevalent is alopecia caused by the male hormone and therefore called androgenic.

Testosterone by a small chemical modification normally occurring in the body changes into an analog, the so-called dihydroxytestosterone (DHT). As an androgen, this compound is much more powerful. One approach to the treatment of hair loss, therefore, has been to inhibit this conversion by a drug. Such a drug has been developed and is currently marketed as Propecia. The effectiveness of Propecia has been reported as varying from 30-50% in arresting hair loss, but clearly there is a disadvantage of a chronic systemic administration and the uncertainty of what changing basic physiological mechanisms may cause. Although there are no such indications in the current clinical studies, no one is certain what manipulation of the normal hormonal turnover in the body will produce after extended use.

It has always been obvious to researchers that an agent acting only on the skin and not penetrating into the body would be much preferable for prevention of hair loss and/or restoration of hair growth. There have been countless attempts to achieve this goal. One drug originally developed to decrease blood pressure, minoxidil, was found to induce upon longer use some hair growth, but only in the vertex area. The efficacy was reported as somewhere around 30%; the effect was attributed to a number of factors, most prominently an incidental increase of blood flow in the scalp. Various vitamins, plant extracts and other preparations were also developed, but none really could overcome the essential effect of the male hormones affecting the hair follicles.

It has been known for a long time that the male hormones can act only after attaching themselves to a messenger, a small protein, the so-called androgen receptor. The androgen receptors can be blocked by certain drugs. These were developed for therapeutic purposes, among others, to keep in check the cancer of the prostate, which squarely depends upon the androgen hormones for its growth. These compounds are given orally and are resorbed from the gut. They act directly by blocking the androgen receptor. It should be noted that such inactivation is always temporary since the cells of our body in their daily cycles continuously manufacture the androgen receptor. Further, there is the problem that androgen receptors are distributed throughout our bodies and are also copious in the brain, where their blockade invariably induces loss of interest in matters of sex, i.e., loss of libido. When applied on the scalp these drugs either had no effect or they were resorbed and passed into the body eliciting systemic side effects. This is why none of these drugs were developed into a safe dermo-cosmetic product to combat hair loss.

In an effort to develop a more powerful inhibitor of the androgen receptor, the biomedical laboratories Biophysica in California, in collaboration with the research laboratories of a Czech biotech pharma company, Interpharma Praha, developed a new class of substances which proved to render the androgen receptor inactive in a novel way. A large number of new molecules were synthesized and tested. Some were not resorbed when given orally or topically. The most promising molecule was structurally modified so that minor amounts of water would cause the molecule's decomposition, thus rendering it pharmacologically inactive and incapable to act inside the body. To prove that this substance, now called Fluridil, once resorbed into the skin would not enter into the body, a number of experimental studies were conducted using rats and rabbits, who are capable of taking up substances through their skin 6 to 10 times more than humans. We applied large quantities of Fluridil, far surpassing the highest conceivable dose in humans. Using sophisticated equipment of high sensitivity no trace of Fluridil or its fragments were ever found in the blood.

Many studies were conducted to ascertain the systemic and topical toxicity in animals and finally in human volunteers at the specialized Experimental Dermatology Institute of the University of California in San Francisco, under the leadership of Professor Howard Maibach. The result of this study was remarkable in that no irritation whatsoever was observed, thus confirming the data we previously gleened from experimental animals.

By then, news had spread and several of our colleagues of ours on their own started applying the compound to their scalp, soon to report the unusual efficacy of the alcoholic solution of Fluridil. We have thereafter optimized the composition of the solution, conducted all required safety tests and after having presented our findings to the authorities, gained marketing approval in the Czech Republic.

In a study with human volunteers, not even trace levels of Fluridil were detected in the serum; therefore, it cannot be expected to have systemic effects. This was also confirmed by the clinical study conducted presently at the Medical School dermatology department (Chairman: J. Bucek, M.D., Palacky University, Olomouc, Czech Republic): in most subjects, increase in anagens (growing hair) and decrease in telogens (dying hair) after 3 months of daily application of 2 ml Fluridil was substantial; there were no changes in the hematological and hormonal profiles and there were no adverse effects.

From what has been said above, it is obvious that the mechanism of Fluridil as a dermo-cosmetic device is sufficiently clear to judge Fluridil's prospective usefulness. Surely, when hair has been missing from the scalp for a long time and the hair follicles were obliterated by the ingrowth of connective tissue, there is very little chance for growing new hair. Here only transplants can reasonably work. Fluridil is therefore useful only when the hair follicles are still active and their androgen receptors are still intact.

So far, the most successful findings were reported by volunteers who started using Fluridil at the time when the first loss of hair was encountered. With men, this can start any time after 30 years of age; with women very often the hair effluvium sometimes dramatically and suddenly appears concurrently with menopause. In these clients we find that the hair loss ceases after a few weeks of once-a-day application.

Perhaps, unfortunately, but understandably based on what had been said above, in order to keep the androgen receptor in check it is necessary to continue applying Fluridil daily. In a number of volunteers we found that after some 3 to 4 months of use, new hair growth, "peach fuzz" - the appearance of baby hair - was induced in the scalp, unless it had been hairless for many years. With time and patience which the hair growth cycle requires - and which may be as long as one year - we often observe a gradual transformation of the "baby hair" into hair of normal appearance.

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