Metronidazole SC Penetrance With Moisturizers

Summary

Topical metronidazole is a widely used first line treatment for erythemotelangiectatic and inflammatory rosacea. Commonly, a moisturizer is also used to restore the skin barrier and reduce inflammation. The purpose of this study is to assess the whether the common practice of applying moisturizer prior to topical metronidazole affects this medication's stratum corneum penetrance in rosacea patients. Participants will have one research office visit that will consist of having a randomly assigned combination of metronidazole and one of four moisturizers applied to their face, followed by non-invasive tape stripping of skin at the 1 hour and 4 hour time points. These tape strip samples will be analyzed with liquid chromatography mass spectrometry (LC-MS) for assessment of metronidazole penetrance in the stratum corneum in the presence of moisturizers. The target population will be rosacea patients in the age range of 18-60 years of age. This study has minimal risks/safety issues as topical metronidazole is an already FDA approved medication with an indication for rosacea and all investigated moisturizers are over-the-counter formulations commonly used within the rosacea patient population. Tape stripping will remove 5 levels of superficial stratum corneum, and will not result in bleeding, scarring, or other prolonged cosmetic disfigurement. Small, transient bruising may result from tape strip collection. The collected samples will have no to minimal biohazard risk, as the collected specimen for analysis will only contain skin scale; samples will be extracted with organic solvents and decontaminated with a 0.2 micron nylon filter prior to analysis on the LC-MS instrumentation.

Timeline

Start

2024-09-03

Primary completion

2025-11-04

Completion

2025-11-04

Publications

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• Background Gallo RL, Granstein RD, Kang S, Mannis M, Steinhoff M, Tan J, Thiboutot D. Rosacea comorbidities and future research: The 2017 update by the National Rosacea Society Expert Committee. J Am Acad Dermatol. 2018 Jan;78(1):167-170. doi: 10.1016/j.jaad.2017.06.150. No abstract available.
• Background Del Rosso JQ, Lehman PA, Raney SG. Impact of order of application of moisturizers on percutaneous absorption kinetics: evaluation of sequential application of moisturizer lotions and azelaic acid gel 15% using a human skin model. Cutis. 2009 Mar;83(3):119-24.
• Background Draelos ZD, Draelos MM, Steele F, Georgiou M, Praestegaard M. Enhanced Skin Deposition of Betamethasone Dipropionate from a Novel Formulation and Drug Delivery Technology. Dermatol Ther (Heidelb). 2023 Aug;13(8):1763-1771. doi: 10.1007/s13555-023-00959-3. Epub 2023 Jun 23.
• Background Draelos ZD, Draelos MM. Development of a Tape-Stripping Liquid Chromatography-Mass Spectrometry Method for Evaluating Skin Deposition of Topical Tazarotene. J Drugs Dermatol. 2021 Oct 1;20(10):1105-1111. doi: 10.36849/JDD.6211.
• Background Gether L, Overgaard LK, Egeberg A, Thyssen JP. Incidence and prevalence of rosacea: a systematic review and meta-analysis. Br J Dermatol. 2018 Aug;179(2):282-289. doi: 10.1111/bjd.16481. Epub 2018 May 31.
• Background Turpeinen M. Absorption of hydrocortisone from the skin reservoir in atopic dermatitis. Br J Dermatol. 1991 Apr;124(4):358-60. doi: 10.1111/j.1365-2133.1991.tb00597.x.
• Background Danby SG, Draelos ZD, Gold LFS, Cha A, Vlahos B, Aikman L, Sanders P, Wu-Linhares D, Cork MJ. Vehicles for atopic dermatitis therapies: more than just a placebo. J Dermatolog Treat. 2022 Mar;33(2):685-698. doi: 10.1080/09546634.2020.1789050. Epub 2020 Jul 16.
• Background Ghadially R, Halkier-Sorensen L, Elias PM. Effects of petrolatum on stratum corneum structure and function. J Am Acad Dermatol. 1992 Mar;26(3 Pt 2):387-96. doi: 10.1016/0190-9622(92)70060-s.
• Background Brand RM, Charron AR, Sandler VL, Jendrzejewski JL. Moisturizing lotions can increase transdermal absorption of the herbicide 2,4-dichlorophenoxacetic acid across hairless mouse skin. Cutan Ocul Toxicol. 2007;26(1):15-23. doi: 10.1080/15569520601182791.
• Background Huh Y, Lee DH, Choi D, Lim KM. Effect of Cosmetics Use on the In Vitro Skin Absorption of a Biocide, 1,2-Benzisothiazolin-3-one. Toxics. 2022 Feb 24;10(3):108. doi: 10.3390/toxics10030108.
• Background Feldmann RJ, Maibach HI. Regional variation in percutaneous penetration of 14C cortisol in man. J Invest Dermatol. 1967 Feb;48(2):181-3. doi: 10.1038/jid.1967.29. No abstract available.
• Background Tipthara P, Kobylinski KC, Godejohann M, Hanboonkunupakarn B, Roth A, Adams JH, White NJ, Jittamala P, Day NPJ, Tarning J. Identification of the metabolites of ivermectin in humans. Pharmacol Res Perspect. 2021 Feb;9(1):e00712. doi: 10.1002/prp2.712.
• Background Vanol PG, Sanyal M, Shah PA, Shrivastav PS. Quantification of metronidazole in human plasma using a highly sensitive and rugged LC-MS/MS method for a bioequivalence study. Biomed Chromatogr. 2018 Aug;32(8):e4242. doi: 10.1002/bmc.4242. Epub 2018 Apr 22.

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