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Novel Formulation Strategy to Improve the Feasibility of Amifostine Administration.
Ranganathan, Kavitha; Simon, Eric; Lynn, Jeremy; Snider, Alicia; Zhang, Yu; Nelson, Noah; Donneys, Alexis; Rodriguez, Jose; Buchman, Lauren; Reyna, Dawn; Lipka, Elke; Buchman, Steven R.
Afiliación
  • Ranganathan K; Department of Plastic Surgery, University of Michigan, 1540 E. Hospital Dr., Floor 4, Suite 4-730, Ann Arbor, Michigan, 48105, USA.
  • Simon E; Therapeutic Systems Research Laboratories, Inc., Ann Arbor, Michigan, USA.
  • Lynn J; Department of Plastic Surgery, University of Michigan, 1540 E. Hospital Dr., Floor 4, Suite 4-730, Ann Arbor, Michigan, 48105, USA.
  • Snider A; Department of Plastic Surgery, University of Michigan, 1540 E. Hospital Dr., Floor 4, Suite 4-730, Ann Arbor, Michigan, 48105, USA.
  • Zhang Y; Department of Plastic Surgery, University of Michigan, 1540 E. Hospital Dr., Floor 4, Suite 4-730, Ann Arbor, Michigan, 48105, USA.
  • Nelson N; Department of Plastic Surgery, University of Michigan, 1540 E. Hospital Dr., Floor 4, Suite 4-730, Ann Arbor, Michigan, 48105, USA.
  • Donneys A; Department of Plastic Surgery, University of Michigan, 1540 E. Hospital Dr., Floor 4, Suite 4-730, Ann Arbor, Michigan, 48105, USA.
  • Rodriguez J; Department of Plastic Surgery, Carilion Clinic, Roanoke, Virginia,, USA.
  • Buchman L; Department of Plastic Surgery, University of Michigan, 1540 E. Hospital Dr., Floor 4, Suite 4-730, Ann Arbor, Michigan, 48105, USA.
  • Reyna D; Therapeutic Systems Research Laboratories, Inc., Ann Arbor, Michigan, USA.
  • Lipka E; Therapeutic Systems Research Laboratories, Inc., Ann Arbor, Michigan, USA.
  • Buchman SR; Department of Plastic Surgery, University of Michigan, 1540 E. Hospital Dr., Floor 4, Suite 4-730, Ann Arbor, Michigan, 48105, USA. sbuchman@med.umich.edu.
Pharm Res ; 35(5): 99, 2018 Mar 19.
Article en En | MEDLINE | ID: mdl-29556791
PURPOSE: Amifostine (AMF), a radioprotectant, is FDA-approved for intravenous administration in cancer patients receiving radiation therapy (XRT). Unfortunately, it remains clinically underutilized due to adverse side effects. The purpose of this study is to define the pharmacokinetic profile of an oral AMF formulation potentially capable of reducing side effects and increasing clinical feasibility. METHODS: Calvarial osteoblasts were radiated under three conditions: no drug, AMF, and WR-1065 (active metabolite). Osteogenic potential of cells was measured using alkaline phosphatase staining. Next, rats were given AMF intravenously or directly into the jejunum, and pharmacokinetic profiles were evaluated. Finally, rats were given AMF orally or subcutaneously, and blood samples were analyzed for pharmacokinetics. RESULTS: WR-1065 preserved osteogenic potential of calvarial osteoblasts after XRT to a greater degree than AMF. Direct jejunal AMF administration incurred a systemic bioavailability of 61.5%. Subcutaneously administrated AMF yielded higher systemic levels, a more rapid peak exposure (0.438 vs. 0.875 h), and greater total systemic exposure of WR-1065 (116,756 vs. 16,874 ng*hr/ml) compared to orally administered AMF. CONCLUSIONS: Orally administered AMF achieves a similar systemic bioavailability and decreased peak plasma level of WR-1065 compared to intravenously administered AMF, suggesting oral AMF formulations maintain radioprotective efficacy without causing onerous side effects, and are clinically feasible.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Osteogénesis / Traumatismos Experimentales por Radiación / Protectores contra Radiación / Amifostina / Mercaptoetilaminas Tipo de estudio: Etiology_studies Límite: Animals / Humans / Male Idioma: En Revista: Pharm Res Año: 2018 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Osteogénesis / Traumatismos Experimentales por Radiación / Protectores contra Radiación / Amifostina / Mercaptoetilaminas Tipo de estudio: Etiology_studies Límite: Animals / Humans / Male Idioma: En Revista: Pharm Res Año: 2018 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos