Prolonged intravenous infusion of sodium nitrite delivers nitric oxide (NO) in humans.
In preclinical studies, infusion of sodium nitrite delivers nitric oxide (NO) as treatment of vasospasm after subarachnoid hemorrhage. We evaluated safety and toxicity of intravenous nitrite administration in healthy volunteers infused with increasing doses of sodium nitrite for 48 h. Twelve volunteers (5 men, 7 women; mean age was 38.8 years, range 27-56 years) participated in the study. The starting sodium nitrite dose was 4.2 mg/kg/h, and it was doubled for each subsequent volunteer up to a maximal dose of 533.8 mg/kg/h at which a clinically silent dose-limiting toxicity (DLT) was observed. Toxicity included a transient decrease of mean arterial blood pressure or asymptomatic increase of methemoglobin level above 5%. The maximal tolerated dose (MTD) was 267 mg/kg/h. S-Nitrosothiols increased significantly in plasma, confirming in vivo sodium nitrite reduction to NO and encouraging its use against vasospasm and ischemia-reperfusion injury to the brain, kidneys, liver, and heart.
National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA. rysiek@ninds.nih.gov
Ryszard M
RM
Pluta
D000328:Adult; D062186:Arterial Pressure / Q000187:drug effects*; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009569:Nitric Oxide / Q000097:blood*; D012977:Sodium Nitrite / Q000008:administration & dosage*; D013997:Time Factors; D055815:Young Adult
D009569:Nitric Oxide; D012977:Sodium Nitrite