Oral Pimonidazole

口服哌莫硝唑

• 批准号: 6787522
• 负责人: JAMES ARTHUR RALEIGH
• 金额: $ 11.19万
• 依托单位: NATURAL PHARMACIA INTERNATIONAL, INC.
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-05-01 至 2005-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6787522
• 关键词: biomarker; biopsy; biotechnology; dogs; drug screening /evaluation; enzyme linked immunosorbent assay; hypoxia; imidazole; immunochemistry; intravenous administration; molecular probes; neoplasm /cancer radiation therapy; nitro compounds; oral administration; pharmacokinetics; technology /technique development

DESCRIPTION (provided by applicant): The patented Hypoxyprobe TM system for measuring tissue hypoxia has been licensed for use in experimental animals. In addition, an FDA IND is available for the clinical application of Hypoxyprobe ru- 1 and the marker is being used in clinics in the US, Canada and Europe. Over 500 patients have received the marker and exciting mechanistic and treatment planning results are being reported. For example, HypoxyproberU-1 (pimonidazole hydrochloride) has predicted local radiation response and has demonstrated the efficacy of an intervention designed to decrease tumor hypoxia during radiation therapy. These successes indicate the value of the Hypoxyprobe TM system. The present proposal is designed to make the marker system even more attractive to patients and clinicians as a routine clinical procedure. The Hypoxyprobe TM procedure is "low tech" and readily incorporated into routine clinical practice. It is well tolerated by patients with no adverse events attributable to the marker. However, intravenous infusion of HypoxyproberM-1 is used and, while most patients tolerate this, we believe that oral administration would improve patient comfort, maximize compliance and set the stage for Hypoxyprobe TM commercialization for companion animal and human use. In the present Phase I application, the safety and efficacy of oral administration of two Hypoxyprobe TM hypoxia markers, HypoxyproberM-1 and HypoxyproberM-F6, will be examined in canine patients in the clinical setting of a Veterinary Hospital. Two experiments are planned. In one, the equivalency of oral and intravenous infusion of the markers in detecting tumor hypoxia will be tested. In the second experiment, the equivalency of the two markers when both are administered orally will be tested. The test will be in the context of a sham irradiation experiment that will set the stage for a detailed examination of the effect of irradiation on tumor hypoxia in a projected Phase II study. Pharmacokinetic studies for the two markers will be carried out in both experiments.

描述（由申请人提供）：用于测量组织缺氧的专利的低氧ProbeTM系统已获得实验动物的使用许可。此外，还可以使用FDA IND进行临床应用HypoxyProbeRu-1，并且标记物用于美国，加拿大和欧洲的诊所。超过500名患者收到了标记和令人兴奋的机械和治疗计划结果。例如，Hypoxyproberu-1（盐酸苯甲酰唑）预测了局部辐射反应，并证明了旨在减少放射治疗期间肿瘤缺氧的干预措施的功效。这些成功表明了低氧Probe TM系统的价值。本提案旨在使标记系统作为常规临床程序对患者和临床医生更具吸引力。 HypoxyProbe TM程序是“低技术”，并且很容易纳入常规临床实践中。没有归因于标记的不良事件的患者可以很好地容忍它。但是，使用了静脉注射静脉输注hyboxyproberm-1，尽管大多数患者容忍这一点，但我们认为口服给药会提高患者舒适性，最大化依从性，并为伴侣动物和人类使用的HypoxyProbe TM商业化奠定了基础。 在目前的I阶段应用中，将在兽医医院的临床环境中检查口服两种低氧Probe TM缺氧标志物（Hypoxyproberm-1和Hypoxyproberm-F6）的安全性和功效。计划了两个实验。在一个中，将测试标志物在检测肿瘤缺氧时的口服和静脉输注的等效性。在第二个实验中，将测试两个标记时两个标记的等效性。该测试将在假辐照实验的背景下，该实验将为预测的II期研究详细检查辐射对肿瘤缺氧的影响奠定基础。在两个实验中将进行两个标记的药代动力学研究。