Advancements in Topical Antifungal Vehicles

February 2016 | Volume 15 | Issue 2 | Supplement Individual Articles | 44 | Copyright © February 2016


Leon H. Kircik MD

Icahn School of Medicine at Mount Sinai, New York, NY;
Indiana University School of Medicine, Indianapolis, IN;
Physicians Skin Care, PLLC, Louisville, KY

epidermis. Sertaconazole nitrate cream penetrated the SC shortly after application, and a relevant amount of the applied dose was recovered from the SC within 30 minutes after its initial application. 29 A plateau of sertaconazole was achieved three hours after administration, and it was maintained for 48 hours.29The estimated average level of sertaconazole nitrate penetration of the SC following the application of 100 milligrams of the cream was 1409 micrograms immediately after application, and it plateaued to 9029 micrograms at 3 hours.29 The relative proportion of sertaconazole penetrating the SC was 1% at 12 hours, 34.2% at 24 hours, and 37.6% after 48 hours.29 Susilo et al concluded that the rapid penetration of sertaconazole nitrate cream into SC and its increasing penetration over time, without significant quantities being distributed into blood, made it a favorable antifungal preparation.29
In 2014, the FDA approved econazole nitrate 1% foam for the treatment of interdigital tinea pedis. Econazole nitrate 1% foam incorporates patented Proderm Technology®, which is a water-lipid based dermal delivery technology that has demonstrated the potential to repair and restore compromised skin barrier function while delivering active ingredients without disrupting skin barrier function.30,31 To assess the safety and efficacy of econazole nitrate 1% foam compared to the foam vehicle for the treatment of interdigital tinea pedis, Elewski and Vlahovic conducted two randomized, double-blind, parallel-group, vehicle-controlled, multicenter trials.31The trials enrolled males and females ≥12 years old with a clinical diagnosis of interdigital tinea pedis who also had a baseline fungal culture that was positive for a dermatophyte.31 The trials’ subjects applied econazole nitrate 1%foam (n=246) or the foam vehicle (n=249) once daily for 4 weeks.31The trails’ primary endpoint was the percentage of subjects achieving a complete cure, which included a negative KOH, negative fungal culture, and a complete resolution of all signs and symptoms at 2 weeks post-treatment or day 43.31 Elewski and Vlahovic found that the complete cure rate by day 43 was 24.3% for the subjects receiving econazole nitrate foam compared to 3.6% for the subjects receiving the foam vehicle. 31 The investigators determined that econazole nitrate foam was highly efficacious over the foam vehicle for the primary and secondary endpoints, and it was safe and well tolerated with a safety profile similar to the foam vehicle. 31

CONCLUSION

Topical anti-fungal treatment for SCFIs is a primary component of the dermatologic armamentarium, and effective treatment of SCFIs depends on both the active drug and the vehicle. The efficacy of topical formulations for SCFIs is not exclusively contingent on the concentration of the active drug but also the vehicle which plays an integral role in the success of topical treatment. Depending on the vehicle, penetration of the active drug can be quite variable. In addition to enhancing an anti-fungal’s effectiveness, a vehicle may itself cause adverse effects, so the development of a vehicle includes multiple considerations. A myriad of diverse and molecularly complex classes of new topical vehicles are continuously being studied and refined in dermatologic research arena.
In this review of topical antifungal vehicles, we found that certain vehicles enhances efficacy up to four weeks post treatment by enabling the retention of the active molecule in the stratum corneum as in the case of naftifine cream and gel. The depo effect in stratum corneum of naftifine or similar agents shortens the treatment period, which increases patient compliance. Additionally, certain properties of vehicles such as ease of use, increase spreadability, and tolerability with a moisturizing effect in case of econazole foam, also increase patient compliance hence efficacy. Thus, we can not emphasize enough the importance of vehicles not only in topical anti fungal treatment but also in all aspects of topical dermatologic therapy.

DISCLOSURES

Dr. Kircik has received funding either as an investigator, speaker, advisory board member, or consultant from Merz, Valeant, and Exeltis.

REFERENCES

  1. Borgers M, Degreef H, Cauwenbergh G. Fungal infections of the skin: infection process and antimycotic therapy. Curr Drug Targets. 2005; 6(8):849 62.
  2. Charles AJ. Superficial cutaneous fungal infections in tropical countries. Dermatol Ther. 2009; 22(6):550-9.
  3. Garber G. An overview of fungal infections. Drugs. 2001;61(Suppl 1):1-12.
  4. Gupta AK, Cooper EA. Update in antifungal therapy of dermatophytosis. Mycopathologia.2008;166(5-6):353-67.
  5. Meis JF, Verweij PE. Current management of fungal infections. Drugs. 2001;61(Suppl 1):13-25.
  6. Zhang, Y, Camp WL, Elewski BE. Advances in topical and systemic antifungals. Clin Dermatol. 2007; 25(2):165-83.
  7. Rotta I, Ziegelmann PK, Otuki MF, et al. Efficacy of topical antifungals in the treatment of dermatophytosis: a mixed-treatment comparison meta-analysis involving 14 treatments. JAMA Dermatol. 2013; 149(3):341-49.
  8. Bouwstra JA, Honeywell-Nguyen PL. Skin structure and mode of action of vesicles. Adv Drug Deliv Rev. 2002;1(54) Suppl 1:S41-55.
  9. Potts RO, Francoeur ML. The influence of stratum corneum morphology on water permeability. J Invest Dermatol. 1991; 96(4):495–99.
  10. Rougier A, Dupuis D, Lotte C, et al. In vivo correlation between stratum corneum reservoir function and percutaneous absorption. J Invest Dermatol. 1983; 81(3):275–78.
  11. Lee CM, Maibach, HI. Deep percutaneous penetration into muscles and joints. Journ of Pharma Sci. 2006; 95(7):1405-12.
  12. Weiss SC. Conventional topical delivery systems. Dermatol Ther. 2011; 24(5):471-6.
  13. Cornell RC, Stoughton RB: Correlation of the vasoconstriction assay and clinical activity in psoriasis. Arch Dermatol.1985; 121:63–7.
  14. Kircik LH. Importance of vehicles in acne therapy. J Drugs Dermatol. 2011; 10(6):s17-23.
  15. Surber C, Smith EW. The mystical effects of dermatological vehicles. Dermatology. 2005; 210(2):157-68.
  16. Feldman SR. Principles of topical treatment: advancement in gel vehicle technology. J Drugs Dermatol. 2014; 13(4):423-27.
  17. Parish LC, Parish JL, Routh HB, et al. A randomized, double-blind, vehicle controlled efficacy and safety study of naftifine 2% cream in the treatment of tinea pedis. J Drugs Dermatol. 2011; 10(11):1282-88.
  18. Parish LC, Parish JL, Routh HB, et al. A double-blind, randomized, vehicle-controlled study evaluating the efficacy and safety of naftifine 2% cream in tinea cruris. J Drugs Dermatol. 2011; 10(10):1142-47.
  19. Monk JP, Brogden RN. Naftifine. A review of its antimicrobial activity and therapeutic use in superficial dermatomycoses. Drugs.1991; 42(4):659-72.
  20. Plaum S, Verma A, Fleischer AB Jr, et al. Detection and relevance of naftifine hydrochloride in the stratum corneum up to four weeks following the last application of naftifine cream and gel, 2%. J Drugs Dermatol. 2013; 12(9):1004-8.
  21. Kircik LH, Onumah N. Use of naftifine hydrochloride 2% cream and 39% urea cream in the treatment of tinea pedis complicated by hyperkeratosis. J Drugs Dermatol. 2014; 13(2):162-5.
Close Menu