Feldman S, Brunner L J
University of Georgia, College of Pharmacy, Department of Pharmaceutics, Athens 30602-2351.
J Clin Pharmacol. 1994 Jun;34(6):677-83. doi: 10.1002/j.1552-4604.1994.tb02023.x.
As the United States seeks a greater presence in space, physiologic changes associated with space flight become of greater concern. Exposure to a weightless environment has been shown to have numerous effects on body composition and organ function. Alterations include decreases in muscle and liver mass, changes in bone structure and integrity, and fluid shifts markedly affecting cardiovascular functioning. Furthermore, metabolic activity of the liver has been found to be altered in rats after extended periods of weightlessness. As the length of space travel increases, the probability for the need to administer pharmacologic agents to crew members during space flight for prophylaxis or treatment becomes greater. Thus, because of the observed physiologic and metabolic changes associated with weightlessness, it is reasonable to assume that the pharmacokinetics and pharmacodynamics of xenobiotics administered during space flight may be different that those found in 1g environment. To address these possible changes, the development of a model of weightlessness to investigate possible alterations in drug pharmacokinetics and pharmacodynamics before space flight is of importance. The tail-suspended rat is a well-described model of weightlessness. During the time of the suspension, the pharmacokinetics of marker compounds can be used to evaluate changes in hepatic and renal physiology. Rats suspended for different periods allow for the investigation of the length of weightlessness exposure and drug pharmacology. Results from the use of the suspended rat model provide valuable information regarding possible pharmacokinetic and pharmacodynamic changes associated with weightlessness, and therefore, provide space biomedical researchers with a method of investigating drug administration during space flight missions.
随着美国寻求在太空扩大存在，与太空飞行相关的生理变化受到了更多关注。已表明暴露于失重环境会对身体组成和器官功能产生诸多影响。这些变化包括肌肉和肝脏质量下降、骨骼结构和完整性改变，以及明显影响心血管功能的体液转移。此外，长时间失重后，已发现大鼠肝脏的代谢活性发生改变。随着太空旅行时间的增加，在太空飞行期间为机组人员进行预防或治疗而给药的可能性也更大。因此，鉴于观察到的与失重相关的生理和代谢变化，可以合理假设在太空飞行期间给予的外源化合物的药代动力学和药效学可能与在1g环境中发现的不同。为了解决这些可能的变化，开发一种失重模型以在太空飞行前研究药物药代动力学和药效学的可能改变具有重要意义。尾部悬吊大鼠是一种描述详尽的失重模型。在悬吊期间，标记化合物的药代动力学可用于评估肝脏和肾脏生理学的变化。悬吊不同时间段的大鼠可用于研究失重暴露时间与药物药理学之间的关系。使用悬吊大鼠模型得到的结果为与失重相关的可能的药代动力学和药效学变化提供了有价值的信息，因此，为太空生物医学研究人员提供了一种在太空飞行任务期间研究药物给药的方法。
