title: Non-invasive analysis of penetration and storage of Isoconazole nitrate in the stratum corneum and the hair follicles.
abstract: Bacteria and fungi are located in the stratum corneum and the hair follicles. Therefore, the development and assessment of efficient drugs requires standard in vivo investigation methods permitting a differentiation between intercellular and follicular penetration and storage of topically applied anti-microbial substances. In the present study, the penetration and storage of Isoconazole nitrate in the stratum corneum and hair follicles was investigated by differential stripping after a 14-day topical application period and during a follow-up period of a further 21 days. One week after the application had terminated, Isoconazole nitrate could still be detected in concentrations above the minimal inhibition concentration in the stratum corneum and the hair follicles. In some subjects, Isoconazole nitrate could even be detected 14 days after the last application. No relevant changes in TEWL values were measured, indicating that the investigated compound did not induce an impairment of the barrier function. The study showed that differential stripping is suited to investigate the penetration and storage of topically applied substances into the stratum corneum and the hair follicles. Also, the hair follicles are a long-term reservoir for topically applied substances. This is of clinical importance, where a long-lasting therapeutic effect beyond the application time is required.
authors.affiliation: Department of Dermatology, Charité - Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Lademann
authors.forename: A
authors.initials: A
authors.lastname: Patzelt
authors.forename: S
authors.initials: S
authors.lastname: Schanzer
authors.forename: H
authors.initials: H
authors.lastname: Richter
authors.forename: G
authors.initials: G
authors.lastname: Thiede
authors.forename: B
authors.initials: B
authors.lastname: Havlickova
authors.forename: C
authors.initials: C
authors.lastname: Günther
authors.forename: M
authors.initials: M
authors.lastname: Friedrich
authors.forename: W
authors.initials: W
authors.lastname: Sterry
authors.forename: J W
authors.initials: JW
authors.lastname: Fluhr
authors.forename: S
authors.initials: S
authors.lastname: Seifert
mesh_terms: D000287:Administration, Topical; D000328:Adult; D000891:Anti-Infective Agents, Local / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D005260:Female; D005500:Follow-Up Studies; D018859:Hair Follicle / Q000378:metabolism*; D006801:Humans; D008297:Male; D008825:Miconazole / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D008826:Microbial Sensitivity Tests / Q000379:methods; D012867:Skin / Q000378:metabolism*; D012869:Skin Absorption; D055815:Young Adult
chemical_list: D000891:Anti-Infective Agents, Local; D008825:Miconazole; C020382:isoconazole