****** DATA-MÉDICOS *********

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LA BUTENAFINA / THE BUTENAFINE

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***** DERMAGIC-EXPRESS No 13 ********

****** 04 NOVIEMBRE 1.998 ******* 

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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 bencilaminas, derivado de las alilaminas con alta actividad fungicida. Schering Plough es el encargado de comercializarlo en Canadá, nombre comercial MENTAX., BUTEMAX, otros

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 Canada, nombre comercial MENTAX y BUTIMEX.

 La butenafina se utiliza para tratar la tiña versicolor causada por Malassezia furfur, así como el pie de atleta (tinea pedis), la tiña corporal y el prurito (tinea vulgaris) causados ​​por los hongos Epidermophytes, Trichophyton trichophyton, Trichophyton rubrum y Trichophyton trichophyton. tratamiento tópico. 

También tiene una actividad más general contra Candida albicans que la terbinafina o la naftifina. La butenafina presenta concentraciones inhibidoras mínimas bajas contra Cryptococcus y Aspergillus. 

Existe  evidencia de que es eficaz contra las infecciones por dermatofitos en las uñas de los pies, pero debe usarse diariamente durante un período prolongado (al menos 1 año) 

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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 proxima edición de DERMAGIC, amigos de la NET,,,

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DERMAGIC/EXPRESS(13)

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L A B U T E N A F I N A 

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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. 

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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. demail@adis.co.nz 

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. 

=====================================================================

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.

agupta@execulink.com 

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-MEDICOS/DERMAGIC-EXPRESS No (13) 04/11/98 DR. JOSE LAPENTA R.

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Produced by Dr. José Lapenta R. Dermatologist
Venezuela 1.998-2.024

Producido por Dr. José Lapenta R. Dermatólogo Venezuela 1.998-2.0024

Tlf: 0414-2976087 - 04127766810