Kamimori G H, Eddington N D, Hoyt R W, Fulco C S, Lugo S, Durkot M J, Brunhart A E, Cymerman A
Department of Behavioral Biology, Walter Reed Army Institute of Research, Washington, DC 20307-5100, USA.
Eur J Clin Pharmacol. 1995;48(2):167-70. doi: 10.1007/BF00192744.
The effects of chronic exposure to high altitude on the pharmacokinetics of caffeine and cardio-green (ICG) were examined in eight healthy males (23-35 y) at sea level (SEA) and following 16 days residence at 4300 m (ALT). ICG (0.5 mg. kg-1) was administered as an intravenous bolus and caffeine (4 mg. kg-1) in an orally ingested solution. The concentration of ICG, caffeine, and the primary metabolites of caffeine (MET) were determined in serial blood samples and their pharmacokinetics computed. In comparison to SEA, ALT resulted in a significant decrease in a caffeine half-life (t1/2, 4.7 vs 6.7 h) and area under the curve (2.5 vs 3.7 g.l-1.min-1), and increased clearance (117 vs 86 ml.min-1.70 kg-1). In ALT the area under the curve the ICG significantly decreased (85 vs 207 mg.l-1.min-1) and the volume of distribution and clearance increased (5.2 vs 2.4 l and 532 vs 234 ml.min-1 respectively) compared to SEA. There was a significant increase in the AUC ratio of MET to caffeine indicating that either metabolite formation or elimination was increased in ALT. These results demonstrate that in humans, chronic exposure to 4300 m results in the modification of the pharmacokinetics of caffeine and ICG.
在海平面（SEA）以及在海拔4300米处（ALT）居住16天后，对8名健康男性（23 - 35岁）进行了研究，以考察长期暴露于高海拔对咖啡因和心绿素（ICG）药代动力学的影响。静脉推注给予ICG（0.5 mg·kg-1），口服摄入咖啡因溶液（4 mg·kg-1）。在系列血样中测定ICG、咖啡因及其咖啡因主要代谢物（MET）的浓度，并计算其药代动力学。与海平面相比，在海拔处咖啡因半衰期（t1/2，4.7对6.7小时）和曲线下面积（2.5对3.7 g·l-1·min-1）显著降低，清除率增加（117对86 ml·min-1·70 kg-1）。与海平面相比，在海拔处ICG的曲线下面积显著降低（85对207 mg·l-1·min-1），分布容积和清除率增加（分别为5.2对2.4升和532对234 ml·min-1）。MET与咖啡因的AUC比值显著增加，表明在海拔处代谢物形成或消除增加。这些结果表明，在人类中，长期暴露于4300米会导致咖啡因和ICG药代动力学的改变。
