EDITORIAL ESPAÑOL:
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Amigos de la red, DERMAGIC los saluda de nuevo, hoy una revisión del nuevo antimicótico que la casa Penederm Incorporated liberó al mercado en 1.997.

Se trata de la BUTENAFINA, un producto perteneciente a las benzylaminas, derivado de las alilaminas con alta actividad fungicida. Schering Plough es el encargado de comercializarlo en Canadá, nombre comercial MENTAX. 
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PRODUCTO:
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Butenafina Hidrocloride al 1 % 
Mentax 1% crema (Schering Plough)
Penederm Incorporated
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Hasta una próxima edición de DERMAGIC, amigos de la NET,,,

Dr. José Lapenta
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DERMAGIC/EXPRESS(12)
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LA BUTENAFINA / THE BUTENAFINE 
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1.) Treatment of interdigital tinea pedis with a 4-week once-daily regimen of butenafine hydrochloride 1% cream. 
2.) One-week therapy with twice-daily butenafine 1% cream versus vehicle in the treatment of tinea pedis: a multicenter, double-blind trial. 
3.) Butenafine 1% cream in the treatment of tinea cruris: a multicenter, vehicle-controlled double-blind trial. 
4.) Butenafine. 
5.) A randomized trial to assess once-daily topical treatment of tinea corporis with butenafine, a new antifungal agent. 
6.) Topical butenafine for tinea pedis. 
7.) Update on topical therapy for superficial fungal infections: focus on butenafine. 
8.) Allylamine type xanthone antimycotics. 
9.) Butenafine, a fungicidal benzylamine derivative, used once daily for the treatment of interdigital tinea pedis. 
10.) Neutral red assay in minimum fungicidal concentrations of antifungal agents. 
11.) Thiophene congeners of morpholine and allylamine type antifungals--syntheses and biological activities. 
12.) LA BUTENAFINA EN LA WEB: Butenafine HCl Approved as OTC Treatment For Athlete's Foot In Canada =====================================================================
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1.)Treatment of interdigital tinea pedis with a 4-week once-daily regimen of butenafine hydrochloride 1% cream. 
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Author 
Tschen E; Elewski B; Gorsulowsky DC; Pariser DM 
Address 
Department of Dermatology, University of New Mexico School of
Medicine, Albuquerque,
USA. 
Source 
J Am Acad Dermatol, 36(2 Pt 1):S9-14 1997 Feb 

Abstract 

BACKGROUND: Butenafine hydrochloride, a potent new benzylamine with fungicidal activity, has been extensively studied and approved for topical use in Japan. Results reported here are from one of the first major North American butenafine clinical trials.

OBJECTIVE: We evaluated butenafine in the treatment of tinea pedis in a controlled, randomized, double-blind trial. METHODS: Of 80 patients with positive fungal cultures, 40 applied butenafine 1% cream and 40 applied vehicle to the affected area once daily for 4 weeks. Efficacy was assessed during treatment and 4 weeks after.

RESULTS: Significantly more patients using butenafine than using vehicle had mycologic cure (butenafine, 88%; vehicle, 33%) and effective clinical response (butenafine, 78%; vehicle, 35%). Differences between treatment groups were greatest (p < 0.001) 4 weeks after treatment.

CONCLUSION: Butenafine applied once daily for 4 weeks resulted in an effective clinical response and mycologic cure of tinea pedis during treatment. Patients continued to improve for at least 4 weeks after treatment. 

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2.) One-week therapy with twice-daily butenafine 1% cream versus vehicle in the treatment of tinea pedis: a multicenter, double-blind trial.  ======================================================================
Author 
Savin R; De Villez RL; Elewski B; Hong S; Jones T; Lowe N; Lucky A; Reyes B; Stewart D; Willis I 
Address 
Department of Dermatology, Yale University School of Medicine, New
Haven, CT, USA. 
Source 
J Am Acad Dermatol, 36(2 Pt 1):S15-9 1997 Feb 

Abstract 
BACKGROUND: Butenafine hydrochloride, a benzylamine derivative with potent antifungal activity, has been used in Japan to treat superficial fungal diseases.

OBJECTIVE: We evaluated the safety and efficacy of twice-daily butenafine versus its vehicle in the treatment of interdigital tinea pedis in a multicenter, randomized, double-blind, parallel-group trial.

METHODS: A total of 402 patients with interdigital tinea pedis and a positive potassium hydroxide examination were enrolled. Of the 271 patients who had culture-confirmed tinea pedis and were assessed for efficacy, 132 applied butenafine and 139 applied vehicle twice daily for 1 week. Patients were assessed for mycologic cure, effective treatment, overall cure, and mycologic/clinical cure.

RESULTS: The rates of all four end points were significantly higher with butenafine than with vehicle 5 weeks after treatment ended. Rates of mycologic cure and effective treatment with butenafine were significantly higher than with vehicle at cessation of treatment. Adverse events to treatment occurred in less than 1% of patients treated with butenafine and 2% of patients who applied vehicle.

CONCLUSION: Butenafine applied twice daily for 1 week is highly effective in treating interdigital tinea
pedis. 
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3.) Butenafine 1% cream in the treatment of tinea cruris: a multicenter, vehicle-controlled double-blind trial. 
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Author 
Lesher JL Jr; Babel DE; Stewart DM; Jones TM; Kaminester L; Goldman M; Weintraub JS 
Address 
Department of Medicine, Medical College of Georgia, Augusta
30912-3190, USA. 
Source 
J Am Acad Dermatol, 36(2 Pt 1):S20-4 1997 Feb 

Abstract 

BACKGROUND: Butenafine hydrochloride, a potent antifungal agent related to the allylamines, has been used in Japan for treating various cutaneous mycoses including tinea cruris.

OBJECTIVE: We compared the safety and efficacy of butenafine hydrochloride and its vehicle when used once daily for 2 weeks to treat tinea cruris.

METHODS: Patients (n = 93) with tinea cruris and a positive potassium hydroxide examination and mycologic culture were enrolled. Of the 76 patients assessed for efficacy, 37 applied butenafine and 39 applied vehicle once daily for 2 weeks. Assessments were made at the end of the 2-week treatment period and 4 weeks after the end of treatment.

RESULTS: Patients in the butenafine group had a higher mycologic cure rate by day 7 (66% vs 13%, p < 0.0001), with marked improvement 4 weeks after the end of treatment (81% vs 13%, p < 0.0001). They also had a higher rate of effective treatment at day 7 (29% vs 5%, p < 0.01) and at 4 weeks after treatment (73% vs 5%, p < 0.0001). Adverse events definitely related to butenafine treatment were limited to one case of burning sensation after application.

CONCLUSION: Butenafine applied once daily for 2 weeks is effective in treating tinea cruris. The proportion of patients cured increased between the end of treatment and 4 weeks after treatment. 

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4.) Butenafine. 
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Author 
McNeely W; Spencer CM 
Address 
Adis International Limited, Auckland, New Zealand. [email protected] 
Source 
Drugs, 55(3):405-12; discussion 413 1998 Mar 

Abstract 

Butenafine is a new antifungal agent with primary fungicidal activity against dermatophytes such as Trichophyton mentagrophytes, Microsporum canis and Trichophyton rubrum which cause tinea infections. 14C-labelled butenafine (approximately 30 micrograms/g tissue) was found within guinea-pig dorsal skin 24 hours after topical application.

Most of the drug was distributed into the epidermis including the horny layer. Small amounts were found in the dermis, probably transported via sebaceous glands and hair follicles. In vitro, the minimum concentration that completely inhibited growth of dermatophytes (MIC) and the minimum fungicidal concentrations (MFC) for butenafine against T. mentagrophytes and M. canis were similar (0.012 to 0.05 mg/L) and were 4 to 130 times lower than those for naftifine, tolnaftate, clotrimazole and bifonazole. It also has greater activity against T. rubrum, M. gypseum and Epidermophyton floccosum when compared with naftifine, tolnaftate and clotrimazole; comparisons with bifonazole against these strains were not available.

Assessment after 1 week's treatment in patients with tinea pedis revealed that mycological cure rates were greater in those who received twice-daily butenafine for 1 week or once-daily butenafine for 4 weeks than in placebo recipients. Mycological and overall cure rates were either further increased or maintained up to 5 weeks after treatment cessation compared with end-of-treatment values. In patients with tinea cruris or tinea corporis who received once-daily butenafine 1% for 2 weeks, the mycological and overall cure rates continued to increase for up to 4 weeks after treatment cessation. 
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5.) A randomized trial to assess once-daily topical treatment of tinea corporis with butenafine, a new antifungal agent. 
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Author 
Greer DL; Weiss J; Rodriguez DA; Hebert AA; Swinehart JM 
Address 
Department of Dermatology, Louisiana State University Medical Center,
New Orleans
70112, USA. 
Source 
J Am Acad Dermatol, 37(2 Pt 1):231-5 1997 Aug 

Abstract 

BACKGROUND: Tinea corporis treatment usually requires topical application of an antifungal agent for 2 to 3 weeks.

OBJECTIVE: We evaluated short-term treatment of tinea corporis with butenafine hydrochloride, a new benzylamine with in vitro fungicidal activity. METHODS: Patients (n = 78) were randomly selected to apply butenafine or its cream vehicle alone once daily for 14 days and were periodically assessed until day 42.

RESULTS: Butenafine recipients had significantly higher rates of mycologic cure beginning at day 7 (64% vs 9%) with continued improvements through day 42 (88% vs 17%). They also had higher rates of effective treatment (mycologic cure and 90% to 100% symptom improvement) at day 7 (33% vs 0%) with increasing rates through day 42 (81% vs 14%).

CONCLUSION: Butenafine provides rapid and persistent antifungal activity and symptom relief in patients with tinea corporis. Significant effects were observed within 7 days of therapy initiation, and increasing effectiveness was observed 4 weeks after therapy. 

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6.) Topical butenafine for tinea pedis.  Source 
Med Lett Drugs Ther, 39(1004):63-4 1997 Jul 4 
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7.) Update on topical therapy for superficial fungal infections: focus on
butenafine. 
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Author 
Odom RB 
Address 
University of California at San Francisco, USA. 
Source 
J Am Acad Dermatol, 36(2 Pt 1):S1-2 1997 Feb 
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8.) Allylamine type xanthone antimycotics. 
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Author 
Salmoiraghi I; Rossi M; Valenti P; Da Re P 
Address 
Institute of Pharmaceutical Chemistry, University of Milan, Italy. 
Source 
Arch Pharm (Weinheim), 331(6):225-7 1998 Jun 

Abstract 

A number of xanthone derivatives bearing the basic chain of naftifine and butenafine antimycotics in 1, 2, 3, and 4 nuclear positions are described. The in vitro antifungal activity against representative strains of molds and yeasts is reported. Only butenafine xanthone analogues show significant activity against Cryptococcus neoformans, in particular the regioisomer 4d (1.5 micrograms/ml). 

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9.) Butenafine, a fungicidal benzylamine derivative, used once daily for the treatment of interdigital tinea pedis. 
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Author 
Reyes BA; Beutner KR; Cullen SI; Rosen T; Shupack JL; Weinstein MB 
Address 
International Dermatology Research, Inc. Miami, Florida, USA. 
Source 
Int J Dermatol, 37(6):450-3 1998 Jun 


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10.) Neutral red assay in minimum fungicidal concentrations of antifungal agents. 
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Author 
Fukuda T; Naka W; Tajima S; Nishikawa T 
Address 
Department of Dermatology, Keio University School of Medicine, Tokyo, Japan. 
Source 
J Med Vet Mycol, 34(5):353-6 1996 Sep-Oct 

Abstract 

We assayed the fungicidal effects of antifungal agents using neutral red staining. Fungal elements of Trichophyton mentagrophytes and T. rubrum were treated with various concentrations of antifungal agents in 96-well filtration plates and then stained with neutral red. The amount of neutral red incorporated by the surviving viable cells was determined from the automated spectrophotometric readings at 550 nm.

The minimum fungicidal concentrations (MFCs) of antifungal agents determined by this assay correlated well with those determined by conventional assay.

This newly developed procedure should provide a rapid, reproducible, quantitative, qualitative and semi-automated susceptibility test for determination of the MFCs of the fungicidal agents. 

Title  An overview of topical antifungal therapy in dermatomycoses. A North American perspective. 

Author  Gupta AK; Einarson TR; Summerbell RC; Shear NH 

 Address  Department of Medicine, Sunnybrook Health Science Center, Toronto, Ontario, Canada. [email protected] 

Source  Drugs, 55(5):645-74 1998 May 

Abstract  Dermatophytes cause fungal infections of keratinised tissues, e.g. skin, hair and nails. The organisms belong to 3 genera, Trichophyton, Epidermophyton and Microsporum. Dermatophytes may be grouped into 3 categories based on host preference and natural habitat. Anthropophilic species predominantly infect humans, geophilic species are soil based and may infect both humans and animals, zoophilic species generally infect non-human mammals. It is important to confirm mycologically the clinical diagnosis of onychomycosis and other tinea infections prior to commencing therapy.

The identity of the fungal organism may provide guidance about the appropriateness of a given topical antifungal agent. Special techniques may be required to obtain the best yield of fungal organisms from a given site, especially the scalp and nails. It is also important to realise the limitations of certain diagnostic aids e.g., Wood's light examination is positive in tinea capitis due to M. canis and M. audouinii (ectothrix organisms); however, Wood's light examination is negative in T. tonsurans (endothrix organism).

Similarly, it is important to be aware that cicloheximide in culture medium will inhibit growth of non-dermatophytes. Appropriate media are therefore required to evaluate the growth of some significant non-dermatophyte moulds. For tinea infections other than tinea capitis and tinea unguium, topical antifungals may be considered. For effective therapy of tinea capitis an oral antifungal is generally necessary. Similarly, oral antifungals are the therapy of choice, especially if onychomycosis is moderate to severe.

Furthermore, where the tinea infection involves a large area, in an immunocompromised host or if infection is recurrent with poor response to topical agents, then oral antifungal therapy may be necessary. Topical antifungal agents may be broadly divided into specific and nonspecific agents. The former group includes the polyenes, azoles, allylamines, amorolfine, ciclopirox and butenafine.

Generally the topical agent is available as a cream, sometimes for use intravaginally. Less commonly, the formulation may be in the form of a powder, lacquer, spray, gel or solution. Many of these agents have a broad spectrum of activity, being effective against dermatophytes, yeasts and Malassezia furfur. For the treatment of tinea corporis, tinea cruris tinea versicolor and cutaneous candidosis, once or twice daily application may be required, the most common duration of therapy being 2 to 4 weeks. For tinea pedis the most common treatment duration is 4 to 6 weeks. 
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11.) Thiophene congeners of morpholine and allylamine type antifungals--syntheses and biological activities. 
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Author 
Bracher F; Papke T 
Address 
Institut f¨ur Pharmazeutische Chemie, Technische Universit¨at
Braunschweig. 
Source 
Pharmazie, 50(8):525-7 1995 Aug 

Abstract 

A thiophene analogue 8 of the antifungal drug amorolfine (1) was prepared starting from the alcohol 5. In addition, congeners of naftifine, terbinafine and butenafine, in which the naphthalene ring is replaced by a branched thienylalkyl group, wee synthesized. Of the four drug analogues only compound 9, related to terbinafine, showed significant antifungal activity.

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12.) Butenafine HCl Approved as OTC Treatment For Athlete's Foot In Canada
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FOSTER CITY, Calif. -- May 8, 1997 --

Penederm Incorporated today announced that its topical antifungal compound, butenafine HCl 1% cream, has received regulatory approval as an over-the-counter (OTC) tinea pedis (athlete's foot) medication from the Health Protection Branch of Health Canada.  Butenafine HCl was recently approved by the United States Food and Drug Administration as a prescription drug for three indications, tinea pedis (athlete'sfoot), tinea corporis (ringworm), and tinea cruris (groin fungus), and is being marketed under the trade name Mentax(tm) (butenafine HCl cream) cream 1% in the United States. 

Schering-Plough Healthcare, Products Inc.will market the butenafine cream in Canada under its own brand names. 

"This is the first OTC approval of our lead topical antifungal," stated Lloyd H. Malchow, President and CEO of Penederm. "We launched Mentax in the US
market early in 1997, along with our co-promotion partner, Schering-Plough Healthcare, Inc. Five papers in the February Journal of the American Academy of Dermatology were recently published in conjunction with our product launch, thereby making available the excellent comprehensive clinical data for this product." 

Malchow went on to say, "We believe that the strong brand franchise Schering-Plough Corporation's subsidiaries hold in OTC antifungals make them an excellent marketing partner for this product." 

Butenafine is the first of a new class of antifungal agents known as the benzylamines, which are chemically and pharmacologically related to the allylamine antifungal drugs. Japan-based Kaken Pharmaceutical Co., Ltd., developed the active compound and markets the drug in Japan, where it has become one of the leading topical antifungals. Penederm acquired exclusive rights to the active compound in Mentax in North, Central and South America for topical use against skin and nail fungus. 

Penederm Incorporated is a specialty pharmaceutical company located in Foster City, California, which focuses on the commercialization of dermatology products. 

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DATA-MÉDICOS/DERMAGIC-EXPRESS No (12) 04/11/98 DR. JOSÉ LAPENTA R.
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