Small animal model of weightlessness for pharmacokinetic evaluation.
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.
Feldman
S
S
University of Georgia, College of Pharmacy, Department of Pharmaceutics, Athens 30602-2351.
Brunner
L J
LJ
D000818:Animals; D006801:Humans; D007668:Kidney / Q000378:metabolism / Q000502:physiology; D008099:Liver / Q000378:metabolism / Q000502:physiology; D008954:Models, Biological; D010599:Pharmacokinetics; D051381:Rats; D014893:Weightlessness / Q000009:adverse effects*