Safety and Ergogenic Properties of Combined Aminophylline and Ambrisentan in Hypoxia.

Journal Article (Journal Article)

We hypothesized that concomitant pharmacological inhibition of the endothelin and adenosine pathway is safe and improves exercise performance in hypoxic humans, via a mechanism that does not involve augmentation of blood oxygenation. To test this hypothesis, we established safety and drug interactions for aminophylline (500 mg) plus ambrisentan (5 mg) in normoxic volunteers. Subsequently, a placebo-controlled study was employed to test the combination in healthy resting and exercising volunteers at simulated altitude (4,267 m). No serious adverse events occurred. Drug interaction was minimal or absent. Aminophylline alleviated hypoxia-induced headaches. Aminophylline, ambrisentan, and their combination all significantly (P < 0.05 vs. placebo) improved submaximal hypoxic exercise performance (19.5, 20.6, and 19.1% >placebo). Single-dose ambrisentan increased blood oxygenation in resting, hypoxic subjects. We conclude that combined aminophylline and ambrisentan offer promise to safely increase exercise capacity in hypoxemic humans without relying on increasing blood oxygen availability.

Full Text

Duke Authors

Cited Authors

  • Schroeder, T; Piantadosi, CA; Natoli, MJ; Autmizguine, J; Cohen-Wolkowieczs, M; Hamilton, KL; Bell, C; Klawitter, J; Christians, U; Irwin, DC; Noveck, RJ

Published Date

  • May 2018

Published In

Volume / Issue

  • 103 / 5

Start / End Page

  • 888 - 898

PubMed ID

  • 28857147

Pubmed Central ID

  • PMC5947522

Electronic International Standard Serial Number (EISSN)

  • 1532-6535

Digital Object Identifier (DOI)

  • 10.1002/cpt.860


  • eng

Conference Location

  • United States