Oral Nitrite and Nitrate in Healthy Normal Volunteer Adults

• Change from baseline in nitrate, nitrite, nitric oxide concentrations over 24 hours [ Time Frame: 0 (trough), then 0.5, 1, 2, 3, 6 and 24 hours post-doses ] [ Designated as safety issue: No ]
  "Post-doses" refers to that subjects will receive a single dose of each study drug, oral 15N-labeled sodium nitrate and nitrite, in random order, separated by a 3-7 day washout period
  
  

• Change from baseline in methemoglobin % over 24 hours [ Time Frame: 0 (trough), then 0.5, 1, 2, 3, 6 and 24 hours post-doses ] [ Designated as safety issue: Yes ]
  "Post-doses" refers to that subjects will receive a single dose of each study drug, oral 15N-labeled sodium nitrate and nitrite, in random order, separated by a 3-7 day washout period
  
  
• Change from baseline in heart rate over 24 hours [ Time Frame: time 0 (trough), every 15 minutes during the first 2 hours post-dose, then at 3, 6, and 24 hours post-dose ] [ Designated as safety issue: No ]
  "Post-dose" refers to that subjects will receive a single dose of each study drug, oral 15N-labeled sodium nitrate and nitrite, in random order, separated by a 3-7 day washout period
  
  
• Change from baseline in mean arterial pressure over 24 hours [ Time Frame: time 0 (trough), every 15 minutes during the first 2 hours post-dose, then at 3, 6, and 24 hours post-dose ] [ Designated as safety issue: Yes ]
  "Post-dose" refers to that subjects will receive a single dose of each study drug, oral 15N-labeled sodium nitrate and nitrite, in random order, separated by a 3-7 day washout period
  
  
• Change from baseline in blood pressure over 24 hours [ Time Frame: time 0 (trough), every 15 minutes during the first 2 hours post-dose, then at 3, 6, and 24 hours post-dose ] [ Designated as safety issue: No ]
  "Post-dose" refers to that subjects will receive a single dose of each study drug, oral 15N-labeled sodium nitrate and nitrite, in random order, separated by a 3-7 day washout period
  
  
• Change from baseline in nitro-fatty acids concentration over 24 hours [ Time Frame: time 0 (trough), every 15 minutes during the first 2 hours post-dose, then at 3, 6, and 24 hours post-dose ] [ Designated as safety issue: No ]
  "Post-dose" refers to that subjects will receive a single dose of each study drug, oral 15N-labeled sodium nitrate and nitrite, in random order, separated by a 3-7 day washout period
  
  
• Change from baseline in platelet mitochondrial function over 24 hours [ Time Frame: 0 (trough) and 6 hours post-dose ] [ Designated as safety issue: No ]
  "Post-dose" refers to that subjects will receive a single dose of each study drug, oral 15N-labeled sodium nitrate and nitrite, in random order, separated by a 3-7 day washout period
  
  

Drug: Non-radioactive "heavy" 15N-labeled sodium nitrite
15N-labeled sodium nitrite 20 mg once
Drug: 15N-labeled sodium nitrate
15N-labeled sodium nitrate 1,000 mg once

Preclinical and clinical research over the last decade has revealed the important vasoprotective effects of nitrates and nitrites with regards to reduction in blood pressure, vascular inflammation and endothelial dysfunction. New findings suggest an effect of nitrate and nitrite therapy in the regulation of glucose-insulin homeostasis. Development of an oral formulation of nitrate and nitrite salts is attractive, whereby nitrite would ensure rapid acting effects upon absorption, while the nitrate would continuously provide a slow formation of nitrite over a prolonged period of time via the enterosalivary circulation pathway.

For this reason, development of an oral formulation of nitrate and nitrite salts is attractive, whereby nitrite would ensure rapid acting effects upon absorption, while the nitrate would continuously provide a slow formation of nitrite over a prolonged period of time via the enterosalivary circulation pathway. This study aims to establish the pharmacokinetics, metabolism and interconversion of nitrate to nitrite and nitrite to nitric oxide in vivo in healthy adult normal volunteers.