6533b825fe1ef96bd1282839
RESEARCH PRODUCT
Safety and Ergogenic Properties of Combined Aminophylline and Ambrisentan in Hypoxia.
Robert J. NoveckJulie AutmizguineDavid IrwinThies SchroederUwe ChristiansMichael J. NatoliChristopher BellKaryn L. HamiltonJelena KlawitterClaude A. PiantadosiMichael Cohen-wolkowieczssubject
AdultMaleAdenosineAmbrisentanAdolescent030204 cardiovascular system & hematologyPharmacologyPlaceboHypoxemia03 medical and health sciencesYoung Adult0302 clinical medicineDouble-Blind MethodmedicineHumansPharmacology (medical)Adverse effectHypoxiaExercisePharmacologyPhenylpropionatesbusiness.industryAltitudeEndothelinsResearchArticlesHypoxia (medical)Drug interactionMiddle AgedAminophylline3. Good healthPyridazinesAnesthesiaAminophyllineDrug Therapy CombinationFemalemedicine.symptomEndothelin receptorbusiness030217 neurology & neurosurgerymedicine.drugSignal Transductiondescription
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 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.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2017-03-24 | Clinical pharmacology and therapeutics |