BIOAVAILABILITY AND PHARMACOTHERAPEUTICS OF PROMETHAZINE IN HUMAN SUBJECTS

异丙嗪在人体中的生物利用度和药物治疗

• 批准号: 7605387
• 负责人: KARL ELMO ANDERSON
• 金额: $ 2.87万
• 依托单位: UNIVERSITY OF TEXAS MED BR GALVESTON
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-04-01 至 2008-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7605387
• 关键词: Adverse effects; Bed rest; Biological Availability; Blood; Clinical Research; Cognitive; Computer Retrieval of Information on Scientific Projects Database; Condition; Data; Diagnosis; Dose; Drowsiness; Environment; Fatigue; Funding; Grant; Institution; Intramuscular; Intramuscular Injections; Investigation; Measures; Methods; Microgravity; Oral; Performance; Pharmaceutical Preparations; Pharmacodynamics; Promethazine; Rate; Rectal Suppositories; Rehabilitation therapy; Reporting; Research; Research Personnel; Resources; Salivary; Source; Space Flight; Space Motion Sickness; Tablets; Techniques; Therapeutic Index; United States National Institutes of Health; absorption; base; human subject; improved; novel; response; stable isotope

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Space motion sickness (SMS) is often treated in space with promethazine (PMZ). Common side effects of PMZ administration (50 mg intramuscular) on the ground are drowsiness and impaired cognitive performance. Anecdotal reports indicate that these effects are absent or less pronounced in space. This suggests that the availability of PMZ to the body (bioavailability) and/or the response of the body to PMZ (pharmacodynamics) may change during space flight. Opportunities for clinical research in space are limited. This is a ground-based research needed to improve, or answer specific questions about, diagnosis and therapy during space flight, and post-flight rehabilitation. We will estimate the bioavailability of an intramuscular injection (IM), oral tablet, and rectal suppository of PMZ in normal subjects during ambulatory and antiorthostatic bed rest (ABR) conditions using novel stable isotope techniques. After three IM doses of PMZ are administered to subjects, we will measure drowsiness, cognitive performance, and salivary flow rate, and will compare them with concentrations of the drug in the blood. We will compare and contrast the bioavailability of PMZ during normal and ABR conditions to examine changes in drug absorption and availability during ABR and evaluate whether these changes may be similar to those anticipated in a microgravity environment. Results of this study will validate methods for an approved in-flight investigation with this medication awaiting an opportunity for manifestation. These data will also provide the much-needed information on the dynamics and therapeutic index of PMZ and their implications on crew fatigue and performance in space.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 太空运动（SMS）经常在异丙嗪（PMZ）中在太空中进行处理。 PMZ给药（50 mg肌肉内）对地面的常见副作用是嗜睡和认知表现受损的。轶事报告表明，这些效应在空间中没有或不太明显。这表明PMZ对人体的可用性（生物利用度）和/或人体对PMZ（药效动力学）的反应可能会在太空飞行期间发生变化。 空间临床研究的机会有限。这是一项基于地面的研究，以改善或回答有关太空飞行期间诊断和治疗的特定问题以及飞行后的康复。 我们将使用新型稳定的同位素技术估计正常受试者中正常受试者中肌内注射（IM），口服片剂和直肠栓剂的生物利用度。 将三剂PMZ施用给受试者后，我们将测量嗜睡，认知表现和唾液流量，并将它们与血液中的药物浓度进行比较。我们将在正常和ABR条件下比较和对比PMZ的生物利用度，以检查ABR期间药物吸收和可用性的变化，并评估这些变化是否可能与微重力环境中预期的变化相似。这项研究的结果将验证对这种药物的批准的机上调查的方法，等待表现的机会。 这些数据还将提供有关PMZ的动态和治疗指数的急需信息及其对船员疲劳和太空性能的影响。