Experimental models in predicting topical antifungal efficacy: practical aspects and challenges.
What are efficient screening models for improved topical antifungals? The use of minimum inhibitory concentrations (MICs) as one such parameter is discussed; we focus on the use of animal membranes for in vitro testing while highlighting the pros and cons of each model, exploring alternatives and discussing the importance of data transferability to humans and the influence of penetration kinetics in topical antifungal efficacy. Ultimately, the gold standard of testing is in vivo in humans; however, initiating with human testing, especially for novel topical antifungal agents, may be impractical, which is why we seek the ideal experimental model that most closely mimics human skin. We conclude that the pig may be an appropriate model membrane for topical antifungal testing based on its similarities in anatomical structure, physiology and permeation to human skin. Most importantly, pig and human skins appear equally permeable to several antifungals in prior in vitro and in vivo work. We do not discuss all prior work but highlight important issues in designing the protocol and parameters of the ideal experimental model for topical antifungals.
Lai
J
J
Department of Dermatology, University of California, San Francisco, CA 94143-0989, USA. jennifer_lai@nymc.edu
Maibach
H I
HI
D000287:Administration, Topical; D000818:Animals; D000935:Antifungal Agents / Q000008:administration & dosage* / Q000378:metabolism; D006801:Humans; D008826:Microbial Sensitivity Tests / Q000379:methods; D023421:Models, Animal; D011237:Predictive Value of Tests; D012867:Skin / Q000187:drug effects / Q000378:metabolism; D012869:Skin Absorption / Q000187:drug effects / Q000502:physiology
D000935:Antifungal Agents