Comparison of oral and transdermal administration of rasagiline mesylate on human melanoma tumor growthin vivo
| Autor: | Richard D. Hamlin, Betsy Huang, Jutaro Shudo, Fatima M. Arjmand, Kevin Dines, Susan R. Meier-Davis, Chad Christianson, Tetsuto Nagata, Jainye Wen |
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| Rok vydání: | 2012 |
| Předmět: |
Drug
Monoamine Oxidase Inhibitors Skin Neoplasms Transdermal patch media_common.quotation_subject Administration Oral Mice Nude Transdermal Patch Antineoplastic Agents Pharmacology Administration Cutaneous Toxicology Melanin Mice chemistry.chemical_compound In vivo medicine Animals Humans Tissue Distribution Melanoma media_common Transdermal Rasagiline business.industry General Medicine medicine.disease Xenograft Model Antitumor Assays Tumor Burden Disease Models Animal chemistry Indans Toxicity Female business |
| Zdroj: | Cutaneous and Ocular Toxicology. 31:312-317 |
| ISSN: | 1556-9535 1556-9527 |
| Popis: | Transdermal patch administration results in a locally high concentration of drug that induce local toxicity, including tumorogenicity. As a worst-case scenario for consequences of repeated application on neoplastic growth, the melanin-binding drug, rasagiline, was used in a transdermal formulation applied directly to a human-derived melanoma to determine the effects on tumor growth.Rasagiline mesylate was administered either orally or transdermally to athymic mice implanted with human melanoma (SKMEL28) to determine the effects on tumor growth and survival. Over a 21-day period, animals were administered daily oral gavage (15 mg/kg) or one or two rasagiline mesylate transdermal patches every 3 days. After the last dose administration, blood samples were collected to confirm drug exposure.All animals from the untreated, vehicle and rasagiline groups survived to the end of the study; however, 7 out of the 10 cisplatin-treated animals died before the end of the study. Rasagiline mesylate dosed either via the oral or transdermal routes had comparable plasma exposure and, unexpectedly, significantly reduced absolute tumor volumes and tumor growth rates in the nude mouse SKMEL28 xenograft model.Transdermal delivery of melanin-binding rasagiline does not increase melanoma growth in the xenograft model. Because rasagiline decreases melanoma growth, it may be candidate for combination therapy for melanoma. |
| Databáze: | OpenAIRE |
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