Brunner L J, DiPiro J T, Feldman S
Department of Pharmaceutics, College of Pharmacy, University of Georgia, Athens, USA.
J Pharmacol Exp Ther. 1995 Jul;274(1):345-52.
As space flight becomes more commonplace, the influence of physiologic changes associated with the microgravity environment become of greater concern. Exposure to weightlessness has been shown to have numerous effects on body composition and organ function in animals and humans. However, studies examining possible alterations in drug metabolism and pharmacokinetics are not readily available. Antipyrine is a marker of hepatic oxidative function and total body water. The purpose of our study was to examine the effects of simulated weightlessness on the pharmacokinetics of antipyrine. Weightlessness was simulated through the use of the tail-suspended rat model. Rats were suspended for a total of 7 days. During the study period, antipyrine pharmacokinetics, after a single 20 mg/kg i.v. or p.o. dose, were evaluated at base line (day-1) and 1, 3 and 7 days after the initiation of suspension. Total body clearance was significantly elevated in the tail suspended rats from both the i.v. and p.o. dosing groups after 3 and 7 days of simulated weightlessness. In addition, clearance was elevated after 1 day of tail-suspension in the p.o. dosing group. Steady-state volume of distribution was not statistically different over the entire study period in either dosing group. Data from the present study suggest that brief periods of tail-suspension may markedly alter the pharmacokinetics of drugs in the rat and that more studies are required in models of weightlessness and actual space flight to understand the complex interaction between microgravity and hepatic metabolic activity.
随着太空飞行变得越来越普遍，与微重力环境相关的生理变化的影响也越来越受到关注。在动物和人类中，暴露于失重环境已被证明会对身体组成和器官功能产生多种影响。然而，关于药物代谢和药代动力学可能改变的研究并不容易获得。安替比林是肝脏氧化功能和全身水含量的标志物。我们研究的目的是检查模拟失重对安替比林药代动力学的影响。通过使用尾部悬吊大鼠模型模拟失重。大鼠总共悬吊7天。在研究期间，在基线（第1天）以及悬吊开始后的第1、3和7天，评估单次静脉注射或口服20 mg/kg剂量后安替比林的药代动力学。模拟失重3天和7天后，静脉注射和口服给药组的尾部悬吊大鼠的全身清除率均显著升高。此外，口服给药组在尾部悬吊1天后清除率升高。在整个研究期间，两个给药组的稳态分布容积在统计学上没有差异。本研究的数据表明，短暂的尾部悬吊可能会显著改变大鼠体内药物的药代动力学，并且需要在失重模型和实际太空飞行中进行更多研究，以了解微重力与肝脏代谢活性之间的复杂相互作用。
