EFFECTS OF ALTITUDE (4300 M) ON THE PHARMACOKINETICS OF CAFFEINE AND CARDIO-GREEN IN HUMANS

The effects of chronic exposure to high altitude on the pharmacokineti cs of caffeine and cardiogreen (ICG) were examined in eight healthy ma les (23-35 y) at sea level (SEA) and following 16 days residence at 43 00 m (ALT). ICG (0.5 mg . kg(-1)) was administered as an intravenous b olus and caffeine (4 mg . kg(-1)) in an orally ingested solution. The concentration of ICG, caffeine, and the primary metabolites of caffein e (MET) were determined in serial blood samples and their pharmacokine tics computed. In comparison to SEA, ALT resulted in a significant dec rease in the caffeine half-life (t(1/2), 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 v s 86 ml . min(-1) 70 kg(-1)). In ALT the area under the curve of ICG s ignificantly decreased (85 vs 207 mg . l(-1). min(-1)) and the volume of distribution and clearance increased (5.2 vs 2.41 and 532 vs 234 ml . min(-1) respectively) compared to SEA. There was a significant incr ease in the AUC ratio of MET to caffeine indicating that either metabo lite formation or elimination was increased in ALT. These results demo nstrate that in humans, chronic exposure to 4300 m results in the modi fication of the pharmacokinetics of caffeine and ICG.