Srinivasan R S, Bourne D W, Putcha L
KRUG Life Sciences, Houston, Texas 77058.
J Clin Pharmacol. 1994 Jun;34(6):692-8. doi: 10.1002/j.1552-4604.1994.tb02025.x.
Exposure to weightlessness induces physiologic changes that may lead to pharmacokinetic and pharmacodynamic alterations of drugs administered to crew members in flight. Preliminary data from flight and ground-based studies indicate that pharmacologically significant changes occur in the kinetics of medications given in weightlessness and in simulated microgravity (head-down bed rest). Conducting flight studies on all available medications to identify the changes in their pharmacokinetic behavior in weightlessness is not feasible. An alternative approach for obtaining such information is to use computer simulations employing physiologically based pharmacokinetic (PBPK) models. Information thus obtained would be helpful in predicting the therapeutic effectiveness of medications in space, and also in developing plans for flight studies. This paper presents a brief review of relevant physiologic factors and pharmacokinetic implications of space flight, and includes a preliminary PBPK model for estimating plasma concentration-time profiles of acetaminophen under different experimental conditions.
暴露于失重环境会引发生理变化，这可能导致给飞行中的机组人员服用的药物出现药代动力学和药效学改变。飞行和地面研究的初步数据表明，在失重和模拟微重力（头低位卧床休息）状态下给药时，药物动力学发生了具有药理学意义的变化。对所有可用药物进行飞行研究以确定其在失重状态下药代动力学行为的变化是不可行的。获取此类信息的另一种方法是使用基于生理的药代动力学（PBPK）模型进行计算机模拟。由此获得的信息将有助于预测药物在太空中的治疗效果，也有助于制定飞行研究计划。本文简要回顾了与太空飞行相关的生理因素和药代动力学影响，并包括一个初步的PBPK模型，用于估计在不同实验条件下对乙酰氨基酚的血浆浓度-时间曲线。
