Acute exposure of the unacclimatized human body to high altitude leads to health
complications, such as loss of exercise performance capacity and fatigue. The investigators
have found that the combination of the xanthine drug theophylline and the endothelin receptor
antagonist ambrisentan improves the exercise performance capacity of rats under simulated
high altitude. In young, healthy human volunteers, this combination of drugs has not increase
toxicity over the single compounds under sea-level conditions. The aim of this study is to
test whether the combination of theophylline, supplied as its more soluble formulation
aminophylline, and ambrisentan, are also safe to take under simulated high altitude of 4,267
meters, under both resting and exercising conditions. The study also aims to test whether
this drug combination improves exercise capacity in humans. In this study, human subjects
will be randomized to one of four treatment sequences and receive the same study drug(s)
throughout all procedures. The study consists of an initial exercise test, followed by two
cycles of drug testing at simulated high altitude: Cycle 1 – resting subjects receiving study
drug at simulated altitude and continually monitored for safety with pharmacodynamic and
pharmacokinetic assessments; and Cycle 2, the same as Cycle 1, with the addition of exercise
testing. It is hypothesized that the combination of aminophylline and ambrisentan is not only
safe under simulated high altitude, but also improves exercise performance capacity, in
comparison with placebo.