Abstract 16779: A Novel Hydrogen Sulfide Donor Promotes Nitric Oxide Bioavailability in a Phase I Clinical Trial
Introduction: Recent studies suggest molecular crosstalk between hydrogen sulfide (H2S) and nitric oxide (NO), although the mechanisms remain poorly understood. Heart failure patients have been reported to be deficient of both H2S and NO, two molecules that are critical for cardiovascular homeostasis. A Phase I clinical trial of a highly novel H2S donor agent (SG-1002) sought to assess the safety of SG-1002 as well as the effects of this drug on H2S and NO bioavailability in healthy subjects.
Methods: 7 healthy male subjects were given SG-1002 orally in dosages ranging from 200-800 mg/kg twice daily for 7d. Plasma samples were collected at incremental time points during a 24hr. period. H2S levels were determined using gas chromatography coupled with sulfur chemiluminescence (7890B and 355 SCD, Agilent Tech.). NO bioavailability was determined by measuring the NO intermediate, nitrite (NO2), using ion chromatography (ENO-30, EICOM USA).
Results: Administration of SG-1002 at the 800 mg/kg, b.i.d. dosage in healthy subjects resulted in significantly increased plasma H2S levels by 30 min post administration (0.22 μM vs. 0.41 μM, p<0.01) and H2S levels remained elevated for a period of 12 hrs (p<0.01 vs. baseline at all time points). Interestingly, nitrite levels, following SG-1002, were significantly increased by 2 hours post administration (0.39 μM vs. 0. 79 μM, p<0.01) and remained elevated through 12 hrs. SG-1002 was well tolerated and safe at all dosages and no serious adverse events were reported in this small clinical trial.
Conclusions: SG-1002 (800 mg/kg) very significantly augmented circulating H2S and plasma nitrite levels in healthy subjects. SG-1002 was well tolerated and safe at all doses tested. These data suggest that SG-1002 not only increases H2S levels, but also significantly increases circulating NO bioavailability. SG-1002 is currently being evaluated in patients with heart failure to assess safety and pharmacokinetics of this highly novel H2S therapy.
Author Disclosures: D.J. Polhemus: None. T. Giordano: Employment; Significant; Significant. Ownership Interest; Significant; Significant. D.J. Lefer: Ownership Interest; Significant; Significant. Consultant/Advisory Board; Significant; Significant.
- © 2014 by American Heart Association, Inc.