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

Publication ,  Journal Article
Schroeder, T; Piantadosi, CA; Natoli, MJ; Autmizguine, J; Cohen-Wolkowieczs, M; Hamilton, KL; Bell, C; Klawitter, J; Christians, U; Irwin, DC ...
Published in: Clin Pharmacol Ther
May 2018

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.

Duke Scholars

Published In

Clin Pharmacol Ther

DOI

EISSN

1532-6535

Publication Date

May 2018

Volume

103

Issue

5

Start / End Page

888 / 898

Location

United States

Related Subject Headings

  • Young Adult
  • Signal Transduction
  • Pyridazines
  • Phenylpropionates
  • Pharmacology & Pharmacy
  • Middle Aged
  • Male
  • Hypoxia
  • Humans
  • Female
 

Citation

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Schroeder, T., Piantadosi, C. A., Natoli, M. J., Autmizguine, J., Cohen-Wolkowieczs, M., Hamilton, K. L., … Noveck, R. J. (2018). Safety and Ergogenic Properties of Combined Aminophylline and Ambrisentan in Hypoxia. Clin Pharmacol Ther, 103(5), 888–898. https://doi.org/10.1002/cpt.860
Schroeder, Thies, Claude A. Piantadosi, Michael J. Natoli, Julie Autmizguine, Michael Cohen-Wolkowieczs, Karyn L. Hamilton, Christopher Bell, et al. “Safety and Ergogenic Properties of Combined Aminophylline and Ambrisentan in Hypoxia.Clin Pharmacol Ther 103, no. 5 (May 2018): 888–98. https://doi.org/10.1002/cpt.860.
Schroeder T, Piantadosi CA, Natoli MJ, Autmizguine J, Cohen-Wolkowieczs M, Hamilton KL, et al. Safety and Ergogenic Properties of Combined Aminophylline and Ambrisentan in Hypoxia. Clin Pharmacol Ther. 2018 May;103(5):888–98.
Schroeder, Thies, et al. “Safety and Ergogenic Properties of Combined Aminophylline and Ambrisentan in Hypoxia.Clin Pharmacol Ther, vol. 103, no. 5, May 2018, pp. 888–98. Pubmed, doi:10.1002/cpt.860.
Schroeder T, Piantadosi CA, Natoli MJ, Autmizguine J, Cohen-Wolkowieczs M, Hamilton KL, Bell C, Klawitter J, Christians U, Irwin DC, Noveck RJ. Safety and Ergogenic Properties of Combined Aminophylline and Ambrisentan in Hypoxia. Clin Pharmacol Ther. 2018 May;103(5):888–898.
Journal cover image

Published In

Clin Pharmacol Ther

DOI

EISSN

1532-6535

Publication Date

May 2018

Volume

103

Issue

5

Start / End Page

888 / 898

Location

United States

Related Subject Headings

  • Young Adult
  • Signal Transduction
  • Pyridazines
  • Phenylpropionates
  • Pharmacology & Pharmacy
  • Middle Aged
  • Male
  • Hypoxia
  • Humans
  • Female