Safety of combined bambuterol and theophylline as a potential treatment of high altitude‐induced fatigue in humans
Abstract
Theophylline is moderately effective against high altitude‐induced malaise, but may be more valuable if combined with other compounds. We hypothesized that theophylline can be combined with a β2 adrenergic receptor (β2AR) agonist in humans to treat high altitude‐induced fatigue. We demonstrate that the β2AR agonist bambuterol alone (high dose = 0.05 mg/kg i.p.) significantly improves exercise performance in rats at simulated high altitude. Combined with theophylline (15 mg/kg), low‐dose bambuterol (0.01 mg/kg) was ergogenic in the same model, whereas theophylline or low‐dose bambuterol alone was not. In a phase‐1 human safety trial, neither single‐dose oral theophylline and bambuterol (Theo‐Dur 400 mg and Bambec 20 mg) nor their combination produced any SAEs. Bambuterol alone decreased plasma potassium (from 3.78 mM to a base average of 3.37 mM), which was not aggravated further by the addition of theophylline (3.83 mM to 3.33 mM). Most frequent AEs were K+max of the bambuterol metabolite terbutaline and delaying t1/2 of theophylline. We conclude that the combination of theophylline and bambuterol is promising and feasible in humans and should undergo testing for safety and efficacy at high altitude.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Apr 01, 2016
- Source ID
- 10.1096/fasebj.30.1_supplement.lb672
Entities
People
- Christopher Bell
- David C. Irwin
- Hasse Z Khiabani
- Karyn Hamilton
- Robert J Noveck
- Thies Schroeder
- Trond‐eirik Strand
Organizations
- Colorado State University
- Defense Advanced Research Projects Agency
- Duke University
- Institute of Aviation, Warsaw
- Johannes Gutenberg University Mainz
- Office of Naval Research
- Oslo University Hospital
- University of Colorado Denver