Skip to main content

Advertisement

SpringerLink
Log in

Synergistic effects of tetrandrine on the antifungal activity of topical ketoconazole cream in the treatment of dermatophytoses: A clinical trial

  • Original Article
  • Published:
Chinese Journal of Integrative Medicine Aims and scope Submit manuscript

Abstract

Objective

To evaluate the synergistic effects of tetrandrine (TET) on the antifungal activity of topical ketoconazole (KCZ) in the treatment of dermatophytoses.

Methods

The minimum inhibitory concentrations (MICs) for KCZ and combined KCZ and TET were compared in vitro. A randomized, double-blind trial was conducted among 97 patients with dermatophytoses who were assigned to 3 groups and received: treatment with combination of 2% KZC and 2% TET cream (KCZ + TET group), or only 2% KZC cream (KCZ group), or 2% TET cream (TET group). Patients with tinea corporis and/or tinea cruris were treated for 2 weeks, separately. The patients with tinea pedis and/or tinea manuum were treated for 4 weeks.

Results

Compared with KZC alone, combined use of KZC and TET showed lower MICs against clinical isolates of dermatophytes (P<0.05 for all). In the patients with tinea corporis and/or tinea cruris, the rates of overall cure (clinical cure plus mycologic clearance) were 81.25% vs. 33.33% for combined treatment and KZC monotherapy, respectively, after 4 weeks. All clinical indices were significantly different between the combination therapy and only KCZ therapy groups (P<0.05). Among the patients with tinea pedis and/or tinea manuum after 4 weeks treatment, the overall cure rates in the KCZ + TET group and KCZ group were 75.00% vs. 40.00%, respectively. In the KCZ + TET group, all the clinical indices were significantly better than those in the KCZ group and TET group (P<0.05). The rates of overall efficacy in the TET group were all zero. No local skin redness or itching was observed during TET treatment. No clinically significant changes were found in post-treatment routine blood, urine, or stool tests, ECG, or tests for liver and kidney function; no serious adverse events occurred.

Conclusion

TET synergistically enhanced the clinical efficacy of topical KZC cream in the treatment of dermatophytoses.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Havlickova B, Czaika VA, Friedrich M. Epidemiological trends in skin mycoses worldwide. Mycoses 2008;51(4):2–15.

    Article  Google Scholar 

  2. Ghannoum MA, Elewski B. Successful treatment of fluconazole-resistant oropharyngeal candidiasis by a combination of fluconazole and terbinafine. Clin Diag Lab Immunol 1999;6:921–923.

    CAS  Google Scholar 

  3. Fohrer C, Fornecker L, Nivoix Y, Cornila C, Marinescu C, Herbrecht R. Antifungal combination treatment: a future perspective. Int J Antimicrob Agents 2006;27(Suppl 1): 25–30.

    Article  PubMed  Google Scholar 

  4. Havlickova B, Friedrich M. The advantages of topical combination therapy in the treatment of inflammatory dermatomycoses. Mycoses 2008;51(14):16–26.

    Article  PubMed  CAS  Google Scholar 

  5. Li F, Zhang H. In vitro study of the synergistic effect of tetrandrine and fluconazole against Candida albicans. Chin J Dermatol (Chin) 2006;39:454–456.

    CAS  Google Scholar 

  6. Wang K, Zhang H, Jiang H, Shi J, GAO A, He H, et, al. In vivo study on tetrandrine as a synergist to fluconazole in murine model of vaginal candidiasis. Chin J Zoonoses (Chin) 2007;23:474–478.

    Google Scholar 

  7. Gao A, Zhang H, Mo H, Jiang H, Wang K, Chao H. Molecular mechanism of the synergy between tetrandrine and fluconazole against Candida albicans. Chin J Dermatol (Chin) 2008;41:97–100.

    CAS  Google Scholar 

  8. Li F, Zhang H, Shan K. In vitro study on the synergistic effect and mechanism of tetrandrine to fluconazole against hyphal form of Candida albicans. Chin J Zoonoses (Chin) 2009;25:13–16.

    Google Scholar 

  9. Zhang H, Gao A, Li F, Zhang G, Ho HI, Liao W. Mechanism of action of tetrandrine, a natural inhibitor of Candida albicans drug efflux pumps. Yakugaku Zasshi 2009;129:623–630.

    Article  PubMed  CAS  Google Scholar 

  10. Shi J, Zhang H, Zhang Z, Gao A, Wang K. Clinical investigation on the synergistic effect of tetrandrine on the antifungal activity of fluconazole for vulvovaginal candidiasis. Chin J Zoonoses (Chin) 2009;25:1121–1123.

    Google Scholar 

  11. Zhang H, Wang K, Zhang G, Ho HI, Gao A. Synergistic anti-candidal activity of tetrandrine on ketoconazole: an experimental study. Planta Med 2010;76:53–61.

    Article  PubMed  CAS  Google Scholar 

  12. Zhang D, Zhang H, Li H, Li S, Shi J. In vivo study on tetrandrine as a synergist to econazole against Trichophyton mentagrophytes. Chin J Zoonoses (Chin) 2010;26:222–225.

    Google Scholar 

  13. Liu C, Zhang H, Xiang S, Zhang D, Su Y. Experiment on tetrandrine as a synergist to bifonazole against Trichophyton mentagrophytes in vivo. Chin J Dermatovenereol (Chin) 2010;24:207–210.

    Google Scholar 

  14. Ogawa Y, Hiruma M. Dermatophytosis: a summary of dermatomycosis as a proposal for future revision of the guidelines. Nippon Ishinkin Gakkai Zasshi 2009;50:199–205.

    Article  Google Scholar 

  15. Mochizuki T. Diagnosis of cutaneous fungal infection. Jpn J Med Mycol 2009;50:195–198.

    Article  Google Scholar 

  16. Kane J, Summerbell R, Sigler L, Krajden S, Land G. Laboratory handbook of dermatophytes: a clinical guide and laboratory manual of dermatophytes and other filamentous fungi from skin, hair, and nails. Mycopathologia 1999;147:113–114.

    Article  Google Scholar 

  17. CLSI/Clinical and Laboratory Standards Institute — Reference method for broth dilution antifungal susceptibility testing of conidium-forming filamentous fungi. Wayne 2002 (Approved Standard M38-A).

  18. Borelli C, Klövekorn G, Ernst TM, Bödeker RH, Korting HC, Neumeister C. Comparative study of 2% sertaconazole solution and cream formulations in patients with tinea corporis, tinea pedis interdigitalis, or a corresponding candidosis. Am J Clin Dermatol 2007;8:371–378.

    Article  PubMed  Google Scholar 

  19. Ramam M, Prasad HR, Manchanda Y, Khaitan BK, Banerjee U, Mukhopadhyaya A, et al. Randomised controlled trial of topical butenafine in tinea cruris and tinea corporis. Indian J Dermatol Venereol Leprol 2003;69:154–158.

    PubMed  CAS  Google Scholar 

  20. Singal A, Pandhi D, Agrawal S, Das S. Comparative efficacy of topical 1% butenafine and 1% clotrimazole in tinea cruris and tinea corporis: a randomized, double-blind trial. J Dermatol Treat 2005;16:331–335.

    Article  CAS  Google Scholar 

  21. Snelders E, van der Lee HA, Kuijpers J, Rijs AJ, Varga J, Samson RA, et al. Emergence of azole resistance in Aspergillus fumigatus and spread of a single resistance mechanism. Plos Med 2008;5:219.

    Article  Google Scholar 

  22. Wroblewska MM, Swoboda-Kopec E, Rokosz A, Krawczyk E, Marchel H, Luczak M. Epidermiology of clinical isolates of Candida albicans and their susceptibility to triazoles. Int J Antimicrob Agents 2002;20:472–475.

    Article  PubMed  CAS  Google Scholar 

  23. da Matta DA, de Almeida LP, Machado AM, Azevedo AC, Kusano EJ, Travassos NF, et al. Antifungal susceptibility of 1 000 Candida bloodstream isolates to 5 antifungal drugs: results of a multicenter study conducted in São Paulo, Brazil, 1995–2003. Diagn Microbiol Infect Dis 2007;57:399–404.

    Article  PubMed  Google Scholar 

  24. Xu C, Liu W, Chen Z, Wang Y, Xiong Z, Ji Y. Effect of prenatal tetrandrine administration on transforming growth factor-beta1 level in the lung of nitrofen-induced congenital diaphragmatic hernia rat model. J Pediatr Surg 2009;44:1611–1620.

    Article  PubMed  Google Scholar 

  25. Chen B, Sun Q, Wang X, Gao F, Dai Y, Yin Y, et al. Reversal in multidrug resistance by magnetic nanoparticle of Fe3O4 loaded with adriamycin and tetrandrine in K562/A02 leukemic cells. Int J Nanomed 2008;3:277–286.

    CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Dermatology, the First Affiliated Hospital, Jinan University, Guangzhou, 510632, China

    Jian-ping Shi  (石建萍), Hong Zhang  (张 宏), Zhi-dong Zhang  (张志东), Ai-li Gao  (高爱莉) & Shou-bao Xiang  (向守宝)

  2. Department of Dermatology, Shajing People’s Hospital, Shenzhen, Guangdong Province, 518104, China

    Jian-ping Shi  (石建萍)

  3. The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510095, China

    Ge-hua Zhang  (张革化)

Authors
  1. Jian-ping Shi  (石建萍)
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Hong Zhang  (张 宏)
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Zhi-dong Zhang  (张志东)
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ge-hua Zhang  (张革化)
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Ai-li Gao  (高爱莉)
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Shou-bao Xiang  (向守宝)
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Hong Zhang  (张 宏).

Additional information

Supported by the National Natural Science Foundation of China (No. 30972660), Foundation of Science and Technology Planning Project of Guangdong Province, China (No. 2009B030801015 and No. 2008B030301350)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Shi, Jp., Zhang, H., Zhang, Zd. et al. Synergistic effects of tetrandrine on the antifungal activity of topical ketoconazole cream in the treatment of dermatophytoses: A clinical trial. Chin. J. Integr. Med. 17, 499–504 (2011). https://doi.org/10.1007/s11655-010-0782-3

Download citation

  • Received:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11655-010-0782-3

Keywords

Search

Navigation