Advertisement

Drugs

, Volume 29, Issue 4, pp 330–341 | Cite as

Ciclopirox Olamine 1% Cream

A Preliminary Review of its Antimicrobial Activity and Therapeutic Use
  • S. G. Jue
  • G. W. Dawson
  • R. N. Brogden
Drug Evaluation

Summary

Synopsis: Ciclopirox olamine1 is a substituted pyridone antimycotic, unrelated to the imidazole derivatives, with activity against a broad spectrum of dermatophytes, yeasts, actinomycetes, molds, other fungi, and a variety of Gram-positive and Gram-negative bacteria. The efficacy of ciclopirox olamine cream has been demonstrated in open and placebo-controlled studies in patients with superficial dermatophyte or yeast infections, and in double-blind comparative trials in patients with dermatomycoses, topical ciclopirox olamine was comparable to or better than clotrimazole in efficacy and caused a similar number of side effects. Ciclopirox olamine penetrates through fingernails and in preliminary studies has been successfully used in onychomycoses. However, further studies are needed to establish the role of ciclopirox in the treatment of onychomycoses and dermatomycoses relative to that of the more recently introduced antifungal agents.

Antimicrobial Studies: The antimicrobial profile of ciclopirox is broader than that of some antimycotics in that it includes dermatophytes, Candida, and important Gram-positive and Gram-negative bacteria. Against common fungal pathogens, in vitro ciclopirox olamine produces complete inhibition at low concentrations of 1 to 4 mg/L when certain antagonising test substrates are avoided. The activity of ciclopirox, unlike that of clotrimazole and miconazole, is only moderately diminished in the presence of albumin added to the incubation medium. The primary site of action at concentrations below 20 mg/L appears to be the cell membrane, where transmembrane transport at least of amino acids into the fungal cell is blocked. At higher concentrations, ciclopirox alters fungal cell membrane integrity allowing leakage of intracellular material. The latter phenomenon has also been reported with nystatin, clotrimazole and miconazole.

Pharmacokinetic Studies: Following topical application of ciclopirox olamine (36 to 37mg) as 1% cream to human skin about 1.3% of the dose is absorbed systemically. Peak serum concentrations reach 0.01 mg/L 6 hours after application. In cadaverous skin, concentrations inhibitory for tested fungi are present within 1 to 2 hours after application and are maintained in the epidermis during the application period. Following application of radiolabelled ciclopirox olamine to human skin, most radioactivity is found on the skin surface, in the hair follicles, and uppermost skin layers. Ciclopirox olamine penetrates through the fingernail. Ciclopirox is excreted in urine with approximately 80% of an oral dose excreted as the glucuronide metabolite.

Therapeutic Trials: Open and a few controlled trials in patients with dermatomycoses have revealed that ciclopirox olamine is more effective than placebo and at least as effective as clotrimazole. Controlled trials have yet to be conducted to compare ciclopirox with tolnaftate, miconazole, or other antifungal agents. The overall profile and incidence of side effects for ciclopirox olamine is similar to clotrimazole. Preliminary studies in onychomycoses have indicated potential usefulness of ciclopirox in this difficult-to-treat infection and of the vaginal cream in the therapy of vaginal and vulvovaginal candidal infection.

Side Effects: In clinical trials, side effects occurred in 1 to 4% of patients and were limited to irritation, redness, pain, burning or itching. In very few patients, treatment was discontinued because of irritation of unknown origin.

Dosage and Administration: In dermatological infections, ciclopirox olamine 1% cream is applied twice daily and gently rubbed into the affected and surrounding skin area. Clinical improvement can occur within the first week of treatment, but if no clinical improvement has occurred after 4 weeks of treatment (2 weeks for tinea versicolor), the diagnosis should be re-examined.

Keywords

Candidiasis Clotrimazole Dermatophytosis Preliminary Review Tinea Pedis 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Adam, W.; Peil, H.G.; Savopoulos, C. and Vanderbeke, O.: Clinical results with the antimycotic agent ciclopirox olamine. Arzneimittel-Forschung 31(II): 1360 (1981).PubMedGoogle Scholar
  2. Alpermann, H.G. and Schütz, E.: Zur Pharmakologie und Toxikologie von Ciclopiroxolamin. Arzneimittel-Forschung 31(II): 1328–1332 (1981).PubMedGoogle Scholar
  3. Azambuja, R.D.: Avaliaçao clinica de ciclopirox creme no tratamento das micoses superficiais. Revista Brasileira de Clinica e Terapêutica 37: 386 (1980).Google Scholar
  4. Barcaui, A. and Lima, A.F.: Estudo clinico com ciclopirox creme no tratamento das dermatomicoses. Revista Brasileira de Clinica e Terapêutica 9: 427 (1980).Google Scholar
  5. Dittmar, W.: Ciclopiroxolamine in dermatomycoses. Proceedings of the 13th International Congress of Chemotherapy (1983).Google Scholar
  6. Dittmar, W.: Contribution to the methodology of testing topical antimycotic agents in guinea-pig dermatophytosis. Mykosen 18: 351 (1975).PubMedGoogle Scholar
  7. Dittmar, W. and Grau, W.: Ciclopirox-substanz mit Aspekten für Mykologie und Kosmetik. Arztliche Kosmetologie 9: 209–214 (1979).Google Scholar
  8. Dittmar, W. and Jović, N.: Microbiological penetration studies on ciclopirox and imidazole antimycotics using postmortem skin. Proceedings of the 15th International Congress of Dermatology, Mexico City (1977).Google Scholar
  9. Dittmar, W. and Lohaus, G.: HOE 296, a new antimycotic compound with a broad antimicrobial spectrum: Laboratory results. Arzneimittel-Forschung 23: 670 (1973).PubMedGoogle Scholar
  10. Dittmar, W.; Grau, W.; Raether, W.; Schrinner, E. and Wagner, W.H.: Mikrobiologische Laborunterschungen mit Ciclopiroxolamin. Arzneimittel-Forschung 31(II): 1317 (1981).PubMedGoogle Scholar
  11. Engst, R. and Krempl-Lamprecht, L.: In vitro studies on the sensitivity of Pityrosporum orbiculare to new antifungal agents. Deutsche Dermatologe 31: 1019–1027 (1983).Google Scholar
  12. Fredriksson, T. and Savopoulos, C: Doppelblind-vergleichsstudie mit ciclopiroxolamine creme und plazebo creme bei derma-tophytosen. Arzneimitel-Forschung 31(11): 1376 (1981).Google Scholar
  13. Kagawa, S.: Clinical effect of ciclopirox olamine (Batrafen) cream on superficial dermatophytosis and skin candidiasis. Nishinihon Journal of Dermatology 40: 362 (1978).CrossRefGoogle Scholar
  14. Kellner, H.M.; Arnold, C; Christ, O.E.; Eckert, H.G.; Herok, J.; Hornke, I. and Rupp, W.: Untersuchungen zur Pharmakokinetik und Biotransformation des Antimykotikums Ciclopiroxolamin bei Tieren und beim Menschen nach topischer und systemischer Anwendung. Arzneimittel-Forschung 31(II): 1338 (1981).Google Scholar
  15. Matsumoto, T. and Urabe, H.: Clinical evaluation of antifungal agents on superficial candidiasis of the skin: Comparison of ciclopirox olamine cream with clotrimazole cream. Nishinihon Journal of Dermatology 40: 345 (1978).CrossRefGoogle Scholar
  16. Miyamoto, M.; Ohtsu, M.; Sugisaki, T. and Takayama, K.: Teratological studies of 6-cyclohexyl-l-hydroxy-4-methyl-2-(lH)-pyridone ethanolamine sale (Hoe 296) in mice and rats (Translation). Pharmacometrics (Tokyo) 9: 67 (1975a).Google Scholar
  17. Mizukami, K.; Hayashi, S.; Omosu, M. and Morioka, H.: Subacute toxicity of 6-cyclohexyl-l-hydroxy-4-methyl-2-(lH)-pyridone ethanolamine sale (Hoe 296) in mice and rats (Translation). Pharmacometrics (Tokyo) 9: 97 (1975a).Google Scholar
  18. Mizukami, K.; Hayashi, S.; Omosu, M. and Moriaka, H.: Influence of the consecutive dermal application of 6-cyclohexyl-l-hydroxy-4-methyl-2-(lH)-pyridone ethanolamine sale (Hoe 296) to beagle dogs for 6 months (Translation). Pharmacometrics (Tokyo) 9: 83 (1975b).Google Scholar
  19. Nishikawa, T.; Ikutomi, M. and Harada, T.: Clinical evaluation of ciclopirox olamine cream on cutaneous candidiasis. Nishinihon Journal of Dermatology 40: 356 (1978).CrossRefGoogle Scholar
  20. Peil, H.G.: Offene Studie zur Wirksamkeit und Vertraglichkeit von Ciclopiroxolamin bei vulvovaginaler Candidose. Arzneimittel-Forschung 31(II): 1366 (1981).PubMedGoogle Scholar
  21. Qadripur, S.A. and Hoehler, T.: Initial results on the topical effectiveness of ciclopirox olamine in onychomycosis. Proceedings of the 8th Congress of the International Society for Human and Animal Mycology, February 8–12 (1982).Google Scholar
  22. Qadripur, S.-A.; Horn, G. and Hohler, T.: Zur Lokalwirksamkeit von Ciclopiroxamin bei Nagelmykosen. Arnzeimittel-For-schung 31(II): 1369 (1981).Google Scholar
  23. Queiroz, J.L. de and Cymbalista, N.B.: Estudo clinico com ciclopirox creme vaginal na candidiase vulvovaginal. Revista Brasileira Clinica e Terapêutica 37: 479 (1980).Google Scholar
  24. Sakurai, M.; Kitatahi, T.; Yoshida, S.; Komine, I. and Fujimoto, K.: Pharmacological study of 6-cyclohexyl-l-hydroxy-4-methyl-2-(lH)-pyridone ethanolamine salt (HOE 296). Pharmacometrics (Oyo Yakuri) 9: 57–65 (1975).Google Scholar
  25. Sakurai, K.; Sakaguchi, T.; Yamaguchi, H. and Iwata, K.: Mode of action of 6-cyclohexyl-l-hydroxy-4-methyl-2-(lH)-pyridone ethanolamine salt (Hoe 296). Chemotherapy 24: 68 (1978a).PubMedCrossRefGoogle Scholar
  26. Sakurai, K.; Sakaguchi, T.; Yamaguchi, H. and Iwata, K.: Studies on the uptake of 6-cyclohexyl-l-hydroxy-4-methyl-2-(lH)-pyridone ethanolamine sale (Hoe 296) by Candida albicans. Chemotherapy 24: 146 (1978b).PubMedCrossRefGoogle Scholar
  27. Shimazaki, T.: Clinical Evaluation of ciclopirox olamine on tinea cruris. Nichinihon Journal of Dermatology 40: 351 (1978a).CrossRefGoogle Scholar
  28. Shimazaki, T.: Clinical evaluation of ciclopirox olamine on superficial candidiasis. Nishinihon Journal of Dermatology 40: 359 (1978b).CrossRefGoogle Scholar
  29. Stachiewicz, E. and Quastel, J.H.: Amino acid transport in yeasts and effects of nystatin. Canadian Journal of Biochemistry and Physiology 41: 397 (1963).PubMedCrossRefGoogle Scholar
  30. Stoughton, R.B.: Skin penetration of HOE 296 vaginal cream compared with Lotrimin 1% cream and Micatin cream (Data on file, Hoechst).Google Scholar
  31. Tarle, S.F.: Estudo comparativo duplo-cego com ciclopirox e clotrimazol sob as formas de creme no tratamento das micoses superficiais. Revista Brasileira de Medicina 37: 316 (1980).Google Scholar
  32. Wajnberg, M. and Wajnberg, A.: Doppelblind-vergleichsstudie mit Ciclopiroxolamin- und Miconazol-vaginalcreme bei vulvovaginaler Candidose. Mykosen 24: 721 (1981).PubMedGoogle Scholar
  33. Weithmann, K.U.: Biochemische Untersuchungen zur Beeinflussung des Prostaglandin- und leukotrien-metabolismus durch Ciclopiroxolamin. Presented at 17th Scientific Meeting of the German-speaking Mycological Society, Luxembourg (1983).Google Scholar
  34. Yamaguchi, H. and Iwata, K.: Effects of three synthetic antimycotics, clotrimazole, miconazole and Hoe 296, on uptake of several substances in C. albicans cells. Japanese Journal of Bacteriology 30: 353 (1975).Google Scholar

Copyright information

© ADIS Press Limited 1985

Authors and Affiliations

  • S. G. Jue
    • 1
    • 2
    • 3
  • G. W. Dawson
    • 1
    • 2
    • 3
  • R. N. Brogden
    • 1
    • 2
    • 3
  1. 1.Clinical Pharmacology UnitVeterans Administration Medical CenterBoiseUSA
  2. 2.Treasure Valley Pharmaceutical ServicesBoiseUSA
  3. 3.ADIS Drug Information ServicesAucklandNew Zealand

Personalised recommendations