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Hypoxy Probe TM系统已获得在实验动物中使用的许可。此外，FDA的IND还可用于次氧探针Ru-1的临床应用，该标记正在美国、加拿大和欧洲的临床上使用。已有500多名患者接受了标记，并报告了令人兴奋的机制和治疗计划结果。例如，Hypoxy proberU-1(盐酸匹莫硝唑)已经预测了局部放射反应，并证明了旨在减少放射治疗期间肿瘤缺氧的干预措施的有效性。这些成功表明了Hypoxy Probe TM系统的价值。目前的建议旨在使标记系统作为一种常规的临床程序对患者和临床医生更具吸引力。 Hypoxy Probe TM程序是“低技术”的，很容易被纳入常规临床实践。患者对它的耐受性很好，没有任何可归因于该标记物的不良事件。然而，使用的是静脉输注Hypoxy proberM-1，虽然大多数患者对此都能耐受，但我们相信口服给药将改善患者的舒适度，最大限度地提高依从性，并为Hypoxy Probe TM商业化提供基础，供动物和人类使用。 在目前的第一阶段应用中，将在一家兽医医院的临床环境中对两种Hypoxy Probe TM缺氧标志物HypoxyproberM-1和HypoxyproberM-F6的口服安全性和有效性进行测试。计划进行两项实验。在一项研究中，将测试口服和静脉输注标记物检测肿瘤缺氧的等效性。在第二个实验中，将测试两个标记物在口服时的等价性。这项测试将在假照射实验的背景下进行，该实验将为在计划的第二阶段研究中详细检查照射对肿瘤缺氧的影响奠定基础。这两个标记物的药代动力学研究将在两个实验中进行。