Variables Affecting Delivery of Glycopyrronium Tosylate Through Human Skin In Vitro
| Autor: | Jon Lenn, Franceso Caserta, Hans Hofland |
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| Rok vydání: | 2020 |
| Předmět: |
Time Factors
medicine.drug_class Skin Absorption Human skin Administration Cutaneous Cholinergic Antagonists Tandem Mass Spectrometry Occlusion medicine Anticholinergic Humans Hyperhidrosis In patient Craniofacial Chromatography High Pressure Liquid Skin integumentary system business.industry Foot Abdominal Wall General Medicine Hand Glycopyrrolate In vitro Anatomical sites Skin penetration Anesthesia Axilla medicine.symptom business |
| Zdroj: | Journal of drugs in dermatology : JDD. 19(11) |
| ISSN: | 1545-9616 |
| Popis: | Background Hyperhidrosis is a condition characterized by excessive sweating beyond what is required for normal thermal regulation. It can involve multiple body areas including the axillae, palms, soles, or craniofacial regions. Glycopyrronium tosylate (GT) is a topical anticholinergic approved by the FDA (2018) for treatment of primary axillary hyperhidrosis in patients 9 years and older. Objective Gain insight into variables (anatomical sites, occlusion, exposure time) affecting GT delivery into human skin. Methods Human skin from different anatomical regions (palmar, plantar, axillary, and abdominal skin) was mounted into flow-through diffusion cells (MedFlux-HTr). GT solution (2.4%) was applied at 10 mg/cm2 and the receiving fluid was collected every 2 hours, for 24 hours. GT penetration was determined using LC/MS/MS. The effect of occlusion was assessed by covering the skin with either parafilm or saran wrap, and the effect of exposure time was assessed by incubating the skin for 5, 15, or 60 minutes before washing off the GT from the surface. Results GT delivery through palmar and plantar skin was up to 40-fold lower compared to delivery through axillary or abdominal skin. Occlusion increased GT delivery up to 10-fold. Reducing exposure time from 24 hours to either 5, 15, or 60 minutes, decreased GT flux by 90%. However, occlusion during these varied exposure times was able to restore GT delivery to levels found in the 24-hour exposed, non-occluded control group. Conclusion These in vitro skin penetration studies showed that skin thickness, exposure time, and occlusion substantially influenced GT delivery, potentially impacting clinical trial design. J Drugs Dermatol. 2020;19(11): doi:10.36849/JDD.2020.5062. |
| Databáze: | OpenAIRE |
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