Saivin S, Pavy-Le Traon A, Soulez-LaRivière C, Güell A, Houin G
Laboratoire de Pharmacocinétique et Toxicologie Clinique, Hopital Purpan, Toulouse, France.
Adv Space Biol Med. 1997;6:107-21. doi: 10.1016/s1569-2574(08)60080-5.
The possible pharmacokinetic mechanisms affected by microgravity are listed in Table 5. In studies of pharmacokinetics in humans, one has generally only access to drug concentrations in plasma and urine which are the results of several concurrent mechanisms. During weightlessness, different changes may occur in each step of the drug disposition process. The most important changes need to be identified and then predicted for the main drugs used in space. The use of a drug as a probe (Table 6) will permit to estimate the changes in specific pharmacokinetic parameters during spaceflight. However, this type of studies is technically difficult to carry out in space, but simulation studies on the ground are easier to perform. Two studies of hepatic blood flow showed no changes in this parameter during bedrest, but a more recent study showed changes in lidocaine disposition during a four-day head-down-tilt. Due to the large differences between individuals, pharmacokinetic changes must be fairly large (> 10-20%) to be observed in studies with probes. To detect a small change in weightlessness will require a number of subjects far higher than can be achieved in spaceflight. In summary, spaceflight is known to change many physiological parameters. The pharmacokinetics of drug disposition is determined by the combination of several complex phenomena. Each step of this process may be influenced by physiopathological changes occurring in spaceflight. This review shows how from a theoretical point of view absorption, distribution and elimination of drugs may be affected by weightlessness. The physiological changes most frequently involved in these modifications are the changes in blood flow due to the fluid shift.
表5列出了受微重力影响的可能的药代动力学机制。在人体药代动力学研究中，人们通常只能获取血浆和尿液中的药物浓度，而这些浓度是多种并发机制的结果。在失重状态下，药物处置过程的每个步骤可能会发生不同的变化。需要识别出最重要的变化，然后针对太空中使用的主要药物进行预测。使用一种药物作为探针（表6）将有助于估计太空飞行期间特定药代动力学参数的变化。然而，这类研究在太空中技术上难以开展，但在地面上进行模拟研究则更容易。两项关于肝血流量的研究表明，卧床休息期间该参数没有变化，但最近一项研究表明，在为期四天的头低位倾斜期间利多卡因的处置发生了变化。由于个体之间差异很大，药代动力学变化必须相当大（>10 - 20%）才能在探针研究中观察到。要检测失重状态下的微小变化，所需的受试者数量将远远超过太空飞行所能达到的数量。总之，已知太空飞行会改变许多生理参数。药物处置的药代动力学由多种复杂现象共同决定。这个过程的每个步骤都可能受到太空飞行中发生的生理病理变化的影响。这篇综述展示了从理论角度来看，失重如何可能影响药物的吸收、分布和消除。这些改变中最常涉及的生理变化是由于体液转移导致的血流变化。
