GRISEOFULVIN: A NEWLOOK AT ANOLD DRUG Oscar E. Araujo, Franklin P. Flowers, and Mark M. King
ABSTRACT: Griseofulvin is the oral antifungal agent of choice for the treatment of dermatophytoses, This article reviewsthe history, pharmacokinetics, adversereactions,and traditional therapeutic applications of griseofulvin. In addition, reports since 1960of the use of the drug in the treatmentof Raynaud'sphenomenon, progressive systemicsclerosis, lichenplanus, mycosisfungoides, herpes roster, eosinophilic fasciitis, and molluscumcontagiosumare discussed, notingthe varyingdegreeof therapeutic success. DlCP Ann Pharmacother 1990;24:851-4.
many non-fungal disease states have been published. It has been noted by various researchers and clinicians to be useful in the treatment of other disease states such as lichen planus, leprosy, scleroderma, and Raynaud's disease." These reports of effectiveness are often in the form of case reports from the clinical setting rather than a result of controlled trials.
Meclumism ofAction
GRISEOFULVIN HASBEENONTHE MARKETfor several decades
having as its primary indicated use the treatment of dermatophyte infections. However, in the course of the last 20 years the drug has been reported to be useful in the therapy of a number of non-fungal disease states. The history ofthis versatile medication, its pharmacokinetic properties, and its application in conventional and non-conventional treatment regimens is reviewed.
History In 1939, Oxford et al. published a manuscript reporting an interesting metabolic product of a strain of Penicillium received from Professor Biourge of the University of Louvaine. The name proposed for this new compound was "griseofulvin," since the parent mold was termed Penicilliumgriseofulvum.' Since its original discovery, griseofulvin has been derived from other organisms such as P. janczewskii, P. patulum, and P. raistriki? For the next 20 years, little else was discovered about the new compound until Gentles found that griseofulvin was useful in the treatment of ringworm in guinea pigs.' Following this revelation, a flurry of experiments was conducted on the new compound to determine its effectiveness in the treatment of dermatophytoses, fungal infections that until the advent of griseofulvin were very difficult to treat. The first experiments of the use of griseofulvin in humans were conducted in 1958 in Germany, Great Britain, and the United States." Since the 1960s, reports of the use of griseofulvin in OSCAR E. ARAUJO, Ph.D., is a Professor, DepartmentofPhannacy Practice,College of Phannacy; FRANKLIN P. FLOWERS, M.D., is an AssociateProfessorof Medicine, Division of Dermatology, Departmentof Medicine, College of Medicine, University of florida, Gainesville, A..; and MARK M. KING, Phann.D., is a Community Pharmacist,Bartow,A... Reprints: Oscar E. Araujo,Ph.D., Box1-486,JHMHC, Gainesville, A.. 32610.
This article is approved for continuing education credit.
Even at high concentrations, griseofulvin is fungistatic and not fungicidal. 4 It was first believed that the mechanism of action of griseofulvin was the disruption of the synthesis of chitin, a compound in fungal cell walls." The actual mechanism of action is still unknown, however, several theories have been proposed. One theory holds that the mechanism of action of griseofulvin lies in its ability to disrupt the mitotic spindle structure, thus arresting the fungal cell growth in the M-phase of its life cycle. Another proposed mechanism suggests that griseofulvin may lead to the production of defective DNA, resulting in an inability of the fungal cells to replicate. 4,5 The reason an oral dose of griseofulvin is effective against a fungal infection lying in the skin is that the drug tends to be deposited in keratin precursor cells. 5 Griseofulvin also shows a preference for infected cells instead of healthy ones." In addition to its antifungal actions, griseofulvin also displays certain antiinflammatory and minor vasodilatory effects. 5
Pharmacokinetics ABSORPTION
The absorption of griseofulvin following oral dosing is variable. The white, bitter compound is virtually insoluble in water, diluted acid, or alkali. In vivo, the drug is mostly absorbed from the duodenum, although it can also be absorbed from the jejunum and ileum. 4-6 The absorption of griseofulvin is enhanced by the reduction of the particle size, thereby increasing the surface area of the compound." Currently, there are two formulations of griseofulvin on the market utilizing different particle sizes, and these ultramicrosize formulations are more rapidly, completely, and uniformly absorbed than the microsize formulations due to the polyethylene glycol added. 5.7 However, despite the claims of manufacturers that ultramicrosize griseofulvin 250 mg is equivalent to 500 mg of the microsize preparations, there have been studies showing that the plasma concentrations of the microsize forms
DICP, The Annals of Pharmacotherapy • 1990September, Volume 24 • 851 Downloaded from aop.sagepub.com at University of Otago Library on December 22, 2014
may be greater over a period of time than those obtained from the ultramicrosize griseofulvin. 4,7 The peak serum concentrations usually achieved following oral administration of 500 mg of microsize or 250 mg of ultramicrosize griseofulvin are 0.4-2.0 IJ.g/mL and occur four to eight hours after administration. 2-5 Other means of increasing the absorption of griseofulvin include the use of a high-fat diet, or preparation of an oil-inwater emulsion of the microsize drug. 4,7 DISTRIBUTION
Upon oral administration, griseofulvin becomes concentrated in the body's skin, hair, nails, liver, fat, and skeletal muscles. 2-6 As mentioned earlier, the drug has a predisposition for deposition into keratin precursor cells, leading to an unfavorable environment for fungal growth. Since the drug also displays an affinity for diseased skin, it is believed that griseofulvin disrupts the fungal cells already present by the disruption of the cell's mitotic spindle structure. 3,5 Griseofulvin appears in the skin approximately four hours after an oral dose at a concentration of 1 IJ.g/g of skin. Eight hours after administration, it is present at a concentration of approximately 3 IJ.g/g. 5 An interesting property of griseofulvin is that more of the drug can be found in the outer layers of the skin than one would suspect from an orally administered preparation. The reason for this property is believed to be that some of the drug is transported to the outer layers via the sweat glands.v"
ELIMINATION The elimination half-life of griseofulvin is variable (924 hours) even within the same patient. 3,6 After an oral dose, 50 percent of the compound is excreted in the urine and 36 percent in the feces within five days.4,6 The major metabolites of griseofulvin are 6-desmethyl-griseofulvin and its glucuronide conjugate. 6
Adverse Reactions The most common adverse effects that occur during griseofulvin therapy are headaches, nausea, vomiting, anorexia, abdominal cramps, flatulence, and diarrhea. Usually, the headache is transient and resolves upon continued use of the drug. 4,5 By taking the medicine with meals, one not only increases the absorption of griseofulvin, but also decreases the gastrointestinal discomforts associated with the compound." One of the more disturbing adverse effects of the drug is the photosensitivity reaction it can induce, which may even lead to a precipitation or exacerbation of lupus erythematoSUS. 4 ,5,8
Hypersensitivity reactions to griseofulvin include urticaria, erythema multiforme, and serum sickness." A case of fatal toxic epidermal necrolysis following the use of griseofulvin has been reported, and is only the second documented case recorded in the literature." Since griseofulvin is derived from species of Penicillium, there is a remote chance of a cross-sensitivity reaction with penicillin. Central nervous system reactions include dizziness, fatigue, and insomnia. On rare occasions, elevations ofporphyrin have been reported with griseofulvin therapy.5
852 •
DICP, The Annals of Pharmacotherapy •
Therapeutic Indications DERMATOPHYTOSES
Since Gentles first reported the effectiveness of griseofulvin in eradicating ringworm infections, the drug has been used in the treatment of a number of fungal infections of the hair and skin, especially tinea corporis, tinea pedis, tinea capitis, tinea barbae, tinea cruris, and tinea unguium. 2-5 Susceptible organisms include species of Trichophyton, Microsporum, or Epidermophyton.r':" The response to therapy with griseofulvin depends on the amount of keratinization present in the infected skin surface along with the time necessary for the natural desquamation process to occur.5,10 Because of the site involved, treatment of fungal infections of the toenails requires many months.v'? Hay et al. demonstrated positive results in the treatment of onychomycoses caused by Trychophyton rubrum by using a topical solution of 28% tioconazole applied twice daily, as adjunctive therapy to oral griseofulvin 500 mg bid. They reported that when the combination of drugs was used as therapy, the chance of complete remission and more rapid improvement was greater than when griseofulvin was used with a base placebo. However, they also noted that despite this combination treatment, 30 percent of the patients being treated with griseofulvin failed to gain complete remission even after a year of therapy. In all cases the patients were followed for one year. Statistically significant differences (p
References I. OXFORD AE, RAlSTRICK H, SIMONART P. Griseofulvin, C. 7H I70.CI, a
metabolic product of Pennicillium Griseo-fulvum Dierckx. Biochem J 1939;33:240-8. 2. ANDERSON DW. Griseofulvin: biology and clinical usefulness. Ann Allergy 1965;23:103-10. 3. GENTLES Jc. Experimental ringworm in guinea pigs: oral treatment with griseofulvin. Nature 1958;182:476-7. 4. BECKER LE.Griseofulvin. DermatolClin 1984;2:115-20. 5. MCEVOY GK, ed. Drug information 88. Bethesda, MD: American Society of Hospital Pharmacists, 1988:76-8. 6. UN C-C,MAGAT J, CHANG R, MCGLOTTEN J, SYMCHOWICZ S. Absorption, metabolism and excretion of 14C-griseofulvin in man. J Pharmacol Exp Ther 1973;187:415-22. 7. STRAUGHN AB,MEYER MC,RAGHOW G, ROTENBERG K. Bioavailability of microsize and ultramicrosize griseofulvin products in man. J Pharmacokinet Biopharm 1980;8:347-62. 8. BLANK H. Commentary: treatment of dermatomycoses with griseofulvin. Arch DermatoI1982;118:834-6. 9. MION G. VERDON R, LEGULLUCHE Y. CARSIN H. GARCIE A, GUlLBAUD 1. Fataltoxicepidermalnecrolysisafter griseofulvin(letter). Lancet 1989;2:1331. 10. HAY RJ,CLAYTON YM, GRIFFITHS WAD, OOWD PM.A comparativedouble blind study of ketoconazole and griseofulvin in dermatophytosis. BrJ DermatoI1985;112:691-6. II. HAY RJ, CLAYTON YM, MOORE MK. A comparison of tioconazole 28% nail solution versus base as an adjunct to oral griseofulvin in patients with onychomycosis. Clin Exp DermatoI1987;12: 175-7. 12. 1J\NZ RR,HEBERT AA.ESTERLY NB.Treatingtinea capitis: should ketoconazole replace griseofulvin? J Pediatr1988;1/2:987-91. 13. SABRI S, ROBERTS VC, HIGGINS RF, COTTON LT, WILLIAMS Dl, WILSON Le. A double-blind clinical trial of griseofulvin in patients with Raynaud's phenomenon. PostgradMed J 1973;49:641-3.
854
•
DICP, The Annals of Pharmacotherapy •
14. FERRI C, BERNINI L, BOMBARDlERI S, PASERO G. Long-term griseofulvin treatment for progressive systemic sclerosis. Scand J Rheumatol 1986;15:356-62. 15. SEHGAL VN, BIKHCHANDANI R, KORANNE RV, NAYAR M, SAXENA HMK. Histopathological evaluation of griseofulvin therapy in lichen planus, a double-blind controlled study. Dermatologica 1980;161: 22-7. 16. LEVY A, STEMPLER D. YUZUK S. SCHEWACH-MILLET M, RONEN M. Communication: treatment of lichen planus with griseofulvin (letter). Int J DermatoI1986;25:405. 17. BAGAN N. SILVESTRE FJ, MESTRE S, GISBERT C, BERMEJO A, AGRAMUNT1. Treatmentof lichen planus with griseofulvin; report of seven cases. Oral SurgMed OralPathoI1985;60:608-10. 18. SHELLEY WB. Demethylchlortetracycline and griseofulvin as examples of specific treatment for mycosis fungoides. Br J Dermatol 1981; 104:477-80. 19. THOMSEN K. Correspondence: mycosis fungoides responding to tetracyclineand griseofulvin (letter). Br J DermatoI1981;105:483-4. 20. JOUBERT JD. Correspondence: griseofulvin in the treatment of herpes zoster (letter). S Afr Med J 1978;54(6):224. 21. CASTELLI M, ZANCA A. GIUBERTONI G, ZANCA A, BERTOLINI A. Griseofulvin-methisoprinol combination in the treatment of herpes zoster. PharmacolRes Commun 1986;18:991-6. 22. GIORDANO M. ARA M, CICALA C, VALENTINI G. CHIANESE U. Correspondence: griseofulvin for eosinophilic fasciitis (letter). Arth RheumatoI1980;23:1331-2. 23. SINGH 01' KANWAR AJ. Griseofulvintherapyin molluscumcontagiosum (letter). Arch DermatoI1977;113: 1615.
EXTRACTO La griseofulvina sigue siendo el agente antift1ngico oral de elecci6n para eI tratamiento de dermat6fitosis. Este articulo revisa la historia, farmacocinetica, reacciones adversas, y aplicaciones terapeuticas tradicionales de la griseofulvina asf como su empleo con resultados variables en el tratamiento del fen6meno de Raynaud, esclerosis sistemica progresiva, liquen plano, micosis fungoides, herpes zoster, fascitis eosinofflica, y molluscum contagiosum. CARMEN CAO
RESUME La griseofulvine est toujours un agent antifongique de choix pour Ie traitement des dermatophytoses. Cet article revise l'historique, la pharmacocinetique, les reactions adverses et les applications therapeutiques traditionnelles de la griseofulvine. De plus on y discute des rapports existants depuis 1960 sur son utilisation dans Ie traitement du phenomene de Raynaud, de la sclerose systemique progressive, du lichen plan, de la mucosite fongoide, de l'herpes zoster, de la fascitite eosinophilique et du molluscum contagiosum en y denotant Ie degre variable de succes therapeutique.
1990 September, Volume 24
Downloaded from aop.sagepub.com at University of Otago Library on December 22, 2014
CHANTAL GUEVREMONT
ABSTRACT: Griseofulvin is the oral antifungal agent of choice for the treatment of dermatophytoses, This article reviewsthe history, pharmacokinetics, adversereactions,and traditional therapeutic applications of griseofulvin. In addition, reports since 1960of the use of the drug in the treatmentof Raynaud'sphenomenon, progressive systemicsclerosis, lichenplanus, mycosisfungoides, herpes roster, eosinophilic fasciitis, and molluscumcontagiosumare discussed, notingthe varyingdegreeof therapeutic success. DlCP Ann Pharmacother 1990;24:851-4.
many non-fungal disease states have been published. It has been noted by various researchers and clinicians to be useful in the treatment of other disease states such as lichen planus, leprosy, scleroderma, and Raynaud's disease." These reports of effectiveness are often in the form of case reports from the clinical setting rather than a result of controlled trials.
Meclumism ofAction
GRISEOFULVIN HASBEENONTHE MARKETfor several decades
having as its primary indicated use the treatment of dermatophyte infections. However, in the course of the last 20 years the drug has been reported to be useful in the therapy of a number of non-fungal disease states. The history ofthis versatile medication, its pharmacokinetic properties, and its application in conventional and non-conventional treatment regimens is reviewed.
History In 1939, Oxford et al. published a manuscript reporting an interesting metabolic product of a strain of Penicillium received from Professor Biourge of the University of Louvaine. The name proposed for this new compound was "griseofulvin," since the parent mold was termed Penicilliumgriseofulvum.' Since its original discovery, griseofulvin has been derived from other organisms such as P. janczewskii, P. patulum, and P. raistriki? For the next 20 years, little else was discovered about the new compound until Gentles found that griseofulvin was useful in the treatment of ringworm in guinea pigs.' Following this revelation, a flurry of experiments was conducted on the new compound to determine its effectiveness in the treatment of dermatophytoses, fungal infections that until the advent of griseofulvin were very difficult to treat. The first experiments of the use of griseofulvin in humans were conducted in 1958 in Germany, Great Britain, and the United States." Since the 1960s, reports of the use of griseofulvin in OSCAR E. ARAUJO, Ph.D., is a Professor, DepartmentofPhannacy Practice,College of Phannacy; FRANKLIN P. FLOWERS, M.D., is an AssociateProfessorof Medicine, Division of Dermatology, Departmentof Medicine, College of Medicine, University of florida, Gainesville, A..; and MARK M. KING, Phann.D., is a Community Pharmacist,Bartow,A... Reprints: Oscar E. Araujo,Ph.D., Box1-486,JHMHC, Gainesville, A.. 32610.
This article is approved for continuing education credit.
Even at high concentrations, griseofulvin is fungistatic and not fungicidal. 4 It was first believed that the mechanism of action of griseofulvin was the disruption of the synthesis of chitin, a compound in fungal cell walls." The actual mechanism of action is still unknown, however, several theories have been proposed. One theory holds that the mechanism of action of griseofulvin lies in its ability to disrupt the mitotic spindle structure, thus arresting the fungal cell growth in the M-phase of its life cycle. Another proposed mechanism suggests that griseofulvin may lead to the production of defective DNA, resulting in an inability of the fungal cells to replicate. 4,5 The reason an oral dose of griseofulvin is effective against a fungal infection lying in the skin is that the drug tends to be deposited in keratin precursor cells. 5 Griseofulvin also shows a preference for infected cells instead of healthy ones." In addition to its antifungal actions, griseofulvin also displays certain antiinflammatory and minor vasodilatory effects. 5
Pharmacokinetics ABSORPTION
The absorption of griseofulvin following oral dosing is variable. The white, bitter compound is virtually insoluble in water, diluted acid, or alkali. In vivo, the drug is mostly absorbed from the duodenum, although it can also be absorbed from the jejunum and ileum. 4-6 The absorption of griseofulvin is enhanced by the reduction of the particle size, thereby increasing the surface area of the compound." Currently, there are two formulations of griseofulvin on the market utilizing different particle sizes, and these ultramicrosize formulations are more rapidly, completely, and uniformly absorbed than the microsize formulations due to the polyethylene glycol added. 5.7 However, despite the claims of manufacturers that ultramicrosize griseofulvin 250 mg is equivalent to 500 mg of the microsize preparations, there have been studies showing that the plasma concentrations of the microsize forms
DICP, The Annals of Pharmacotherapy • 1990September, Volume 24 • 851 Downloaded from aop.sagepub.com at University of Otago Library on December 22, 2014
may be greater over a period of time than those obtained from the ultramicrosize griseofulvin. 4,7 The peak serum concentrations usually achieved following oral administration of 500 mg of microsize or 250 mg of ultramicrosize griseofulvin are 0.4-2.0 IJ.g/mL and occur four to eight hours after administration. 2-5 Other means of increasing the absorption of griseofulvin include the use of a high-fat diet, or preparation of an oil-inwater emulsion of the microsize drug. 4,7 DISTRIBUTION
Upon oral administration, griseofulvin becomes concentrated in the body's skin, hair, nails, liver, fat, and skeletal muscles. 2-6 As mentioned earlier, the drug has a predisposition for deposition into keratin precursor cells, leading to an unfavorable environment for fungal growth. Since the drug also displays an affinity for diseased skin, it is believed that griseofulvin disrupts the fungal cells already present by the disruption of the cell's mitotic spindle structure. 3,5 Griseofulvin appears in the skin approximately four hours after an oral dose at a concentration of 1 IJ.g/g of skin. Eight hours after administration, it is present at a concentration of approximately 3 IJ.g/g. 5 An interesting property of griseofulvin is that more of the drug can be found in the outer layers of the skin than one would suspect from an orally administered preparation. The reason for this property is believed to be that some of the drug is transported to the outer layers via the sweat glands.v"
ELIMINATION The elimination half-life of griseofulvin is variable (924 hours) even within the same patient. 3,6 After an oral dose, 50 percent of the compound is excreted in the urine and 36 percent in the feces within five days.4,6 The major metabolites of griseofulvin are 6-desmethyl-griseofulvin and its glucuronide conjugate. 6
Adverse Reactions The most common adverse effects that occur during griseofulvin therapy are headaches, nausea, vomiting, anorexia, abdominal cramps, flatulence, and diarrhea. Usually, the headache is transient and resolves upon continued use of the drug. 4,5 By taking the medicine with meals, one not only increases the absorption of griseofulvin, but also decreases the gastrointestinal discomforts associated with the compound." One of the more disturbing adverse effects of the drug is the photosensitivity reaction it can induce, which may even lead to a precipitation or exacerbation of lupus erythematoSUS. 4 ,5,8
Hypersensitivity reactions to griseofulvin include urticaria, erythema multiforme, and serum sickness." A case of fatal toxic epidermal necrolysis following the use of griseofulvin has been reported, and is only the second documented case recorded in the literature." Since griseofulvin is derived from species of Penicillium, there is a remote chance of a cross-sensitivity reaction with penicillin. Central nervous system reactions include dizziness, fatigue, and insomnia. On rare occasions, elevations ofporphyrin have been reported with griseofulvin therapy.5
852 •
DICP, The Annals of Pharmacotherapy •
Therapeutic Indications DERMATOPHYTOSES
Since Gentles first reported the effectiveness of griseofulvin in eradicating ringworm infections, the drug has been used in the treatment of a number of fungal infections of the hair and skin, especially tinea corporis, tinea pedis, tinea capitis, tinea barbae, tinea cruris, and tinea unguium. 2-5 Susceptible organisms include species of Trichophyton, Microsporum, or Epidermophyton.r':" The response to therapy with griseofulvin depends on the amount of keratinization present in the infected skin surface along with the time necessary for the natural desquamation process to occur.5,10 Because of the site involved, treatment of fungal infections of the toenails requires many months.v'? Hay et al. demonstrated positive results in the treatment of onychomycoses caused by Trychophyton rubrum by using a topical solution of 28% tioconazole applied twice daily, as adjunctive therapy to oral griseofulvin 500 mg bid. They reported that when the combination of drugs was used as therapy, the chance of complete remission and more rapid improvement was greater than when griseofulvin was used with a base placebo. However, they also noted that despite this combination treatment, 30 percent of the patients being treated with griseofulvin failed to gain complete remission even after a year of therapy. In all cases the patients were followed for one year. Statistically significant differences (p
References I. OXFORD AE, RAlSTRICK H, SIMONART P. Griseofulvin, C. 7H I70.CI, a
metabolic product of Pennicillium Griseo-fulvum Dierckx. Biochem J 1939;33:240-8. 2. ANDERSON DW. Griseofulvin: biology and clinical usefulness. Ann Allergy 1965;23:103-10. 3. GENTLES Jc. Experimental ringworm in guinea pigs: oral treatment with griseofulvin. Nature 1958;182:476-7. 4. BECKER LE.Griseofulvin. DermatolClin 1984;2:115-20. 5. MCEVOY GK, ed. Drug information 88. Bethesda, MD: American Society of Hospital Pharmacists, 1988:76-8. 6. UN C-C,MAGAT J, CHANG R, MCGLOTTEN J, SYMCHOWICZ S. Absorption, metabolism and excretion of 14C-griseofulvin in man. J Pharmacol Exp Ther 1973;187:415-22. 7. STRAUGHN AB,MEYER MC,RAGHOW G, ROTENBERG K. Bioavailability of microsize and ultramicrosize griseofulvin products in man. J Pharmacokinet Biopharm 1980;8:347-62. 8. BLANK H. Commentary: treatment of dermatomycoses with griseofulvin. Arch DermatoI1982;118:834-6. 9. MION G. VERDON R, LEGULLUCHE Y. CARSIN H. GARCIE A, GUlLBAUD 1. Fataltoxicepidermalnecrolysisafter griseofulvin(letter). Lancet 1989;2:1331. 10. HAY RJ,CLAYTON YM, GRIFFITHS WAD, OOWD PM.A comparativedouble blind study of ketoconazole and griseofulvin in dermatophytosis. BrJ DermatoI1985;112:691-6. II. HAY RJ, CLAYTON YM, MOORE MK. A comparison of tioconazole 28% nail solution versus base as an adjunct to oral griseofulvin in patients with onychomycosis. Clin Exp DermatoI1987;12: 175-7. 12. 1J\NZ RR,HEBERT AA.ESTERLY NB.Treatingtinea capitis: should ketoconazole replace griseofulvin? J Pediatr1988;1/2:987-91. 13. SABRI S, ROBERTS VC, HIGGINS RF, COTTON LT, WILLIAMS Dl, WILSON Le. A double-blind clinical trial of griseofulvin in patients with Raynaud's phenomenon. PostgradMed J 1973;49:641-3.
854
•
DICP, The Annals of Pharmacotherapy •
14. FERRI C, BERNINI L, BOMBARDlERI S, PASERO G. Long-term griseofulvin treatment for progressive systemic sclerosis. Scand J Rheumatol 1986;15:356-62. 15. SEHGAL VN, BIKHCHANDANI R, KORANNE RV, NAYAR M, SAXENA HMK. Histopathological evaluation of griseofulvin therapy in lichen planus, a double-blind controlled study. Dermatologica 1980;161: 22-7. 16. LEVY A, STEMPLER D. YUZUK S. SCHEWACH-MILLET M, RONEN M. Communication: treatment of lichen planus with griseofulvin (letter). Int J DermatoI1986;25:405. 17. BAGAN N. SILVESTRE FJ, MESTRE S, GISBERT C, BERMEJO A, AGRAMUNT1. Treatmentof lichen planus with griseofulvin; report of seven cases. Oral SurgMed OralPathoI1985;60:608-10. 18. SHELLEY WB. Demethylchlortetracycline and griseofulvin as examples of specific treatment for mycosis fungoides. Br J Dermatol 1981; 104:477-80. 19. THOMSEN K. Correspondence: mycosis fungoides responding to tetracyclineand griseofulvin (letter). Br J DermatoI1981;105:483-4. 20. JOUBERT JD. Correspondence: griseofulvin in the treatment of herpes zoster (letter). S Afr Med J 1978;54(6):224. 21. CASTELLI M, ZANCA A. GIUBERTONI G, ZANCA A, BERTOLINI A. Griseofulvin-methisoprinol combination in the treatment of herpes zoster. PharmacolRes Commun 1986;18:991-6. 22. GIORDANO M. ARA M, CICALA C, VALENTINI G. CHIANESE U. Correspondence: griseofulvin for eosinophilic fasciitis (letter). Arth RheumatoI1980;23:1331-2. 23. SINGH 01' KANWAR AJ. Griseofulvintherapyin molluscumcontagiosum (letter). Arch DermatoI1977;113: 1615.
EXTRACTO La griseofulvina sigue siendo el agente antift1ngico oral de elecci6n para eI tratamiento de dermat6fitosis. Este articulo revisa la historia, farmacocinetica, reacciones adversas, y aplicaciones terapeuticas tradicionales de la griseofulvina asf como su empleo con resultados variables en el tratamiento del fen6meno de Raynaud, esclerosis sistemica progresiva, liquen plano, micosis fungoides, herpes zoster, fascitis eosinofflica, y molluscum contagiosum. CARMEN CAO
RESUME La griseofulvine est toujours un agent antifongique de choix pour Ie traitement des dermatophytoses. Cet article revise l'historique, la pharmacocinetique, les reactions adverses et les applications therapeutiques traditionnelles de la griseofulvine. De plus on y discute des rapports existants depuis 1960 sur son utilisation dans Ie traitement du phenomene de Raynaud, de la sclerose systemique progressive, du lichen plan, de la mucosite fongoide, de l'herpes zoster, de la fascitite eosinophilique et du molluscum contagiosum en y denotant Ie degre variable de succes therapeutique.
1990 September, Volume 24
Downloaded from aop.sagepub.com at University of Otago Library on December 22, 2014
CHANTAL GUEVREMONT
