Trial reportClinical pharmacokinetics2015
Pharmacokinetics, pharmacodynamics, safety, and tolerability of nebulized sodium nitrite (AIR001) following repeat-dose inhalation in healthy subjects.
Trial report in Clinical pharmacokinetics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01431313 (A Dose Escalation Study to Evaluate the Effect of Inhaled Nitrite on Cardiopulmonary Hemodynamics in Subjects With Pulmonary Hypertension), which is not on this map. Cited by 29 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
A Dose Escalation Study to Evaluate the Effect of Inhaled Nitrite on Cardiopulmonary Hemodynamics in Subjects With Pulmonary Hypertension
Who cites it
29 citing papers in PubMed, 47 citations in OpenAlex.
- Effect of organic and inorganic nitrates on cerebrovascular pulsatile power transmission in patients with heart failure and preserved ejection fraction.Physiological measurement · 2018Trial
- Acute hemodynamic effects of inhaled sodium nitrite in pulmonary hypertension associated with heart failure with preserved ejection fraction.JCI insight · 2016Trial
- Inhaled Sodium Nitrite Improves Rest and Exercise Hemodynamics in Heart Failure With Preserved Ejection Fraction.Circulation research · 2016Trial
- Endothelial and platelet dysfunction in systemic sclerosis with pulmonary hypertension.PloS one · 2026Article
- Decreased Endogenous Nitric Oxide Production in Patients with Acute Decompensated Heart Failure with Preserved Ejection Fraction.Journal of clinical medicine · 2025Article
- Clinical Pharmacokinetics of Inhaled Drugs for Pulmonary Hypertension.Clinical pharmacokinetics · 2025Review
- Increased Anion Exchanger-1 (Band 3) on the Red Blood Cell Membrane Accelerates Scavenging of Nitric Oxide Metabolites and Predisposes Hypertension Risks.Function (Oxford, England) · 2025Article
- Suicidal sodium nitrite intoxication: a case report focusing on the postmortem findings and toxicological analyses-review of the literature.Forensic science, medicine, and pathology · 2024Review
- The hemodynamic response to nitrite is acute and dependent upon tissue perfusion.Nitric oxide : biology and chemistry · 2024Article
- Fractional nitric oxide measurement in exhaled air (FeNO): perspectives in the management of respiratory diseases.Therapeutic advances in chronic disease · 2023Review
- Complex Interplay of Heme-Copper Oxidases with Nitrite and Nitric Oxide.International journal of molecular sciences · 2022Review
- Nitrous anhydrase activity of carbonic anhydrase II: cysteine is required for nitric oxide (NO) dependent phosphorylation of VASP in human platelets.Journal of enzyme inhibition and medicinal chemistry · 2021Article
- Endogenous Hemoprotein-Dependent Signaling Pathways of Nitric Oxide and Nitrite.Inorganic chemistry · 2021Review
- Safety and toxicology assessment of sodium nitrite administered by intramuscular injection.Toxicology and applied pharmacology · 2021Article
- Evidence for placental-derived iron-nitrosyls in the circulation of the fetal lamb and against a role for nitrite in mediating the cardiovascular transition at birth.American journal of physiology. Regulatory, integrative and comparative physiology · 2020Article
- Nitrite modulates aminoglycoside tolerance by inhibiting cytochrome heme-copper oxidase in bacteria.Communications biology · 2020Article
- Inhaled nebulized nitrite and nitrate therapy in a canine model of hypoxia-induced pulmonary hypertension.Nitric oxide : biology and chemistry · 2019Article
- Discontinued Drugs for the Treatment of Cardiovascular Disease from 2016 to 2018.International journal of molecular sciences · 2019Review
- Nitrite and nitrate chemical biology and signalling.British journal of pharmacology · 2019Review
- A pilot study on the kinetics of metabolites and microvascular cutaneous effects of nitric oxide inhalation in healthy volunteers.PloS one · 2019Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 7 institutions in 2 countries.
Funding
Abstract
introductionThe efficacy of nebulized sodium nitrite (AIR001) has been demonstrated in animal models of pulmonary arterial hypertension (PAH), but it was not known if inhaled nitrite would be well tolerated in human subjects at exposure levels associated with efficacy in these models.
methodsInhaled nebulized sodium nitrite was assessed in three independent studies in a total of 82 healthy male and female subjects. Study objectives included determination of the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) under normal and mildly hypoxic conditions, and following co-administration with steady-state sildenafil, assessment of nitrite pharmacokinetics, and evaluation of the fraction exhaled nitric oxide (FENO) and concentrations of iron-nitrosyl hemoglobin (Hb(Fe)-NO) and S-nitrosothiols (R-SNO) as biomarkers of local and systemic NO exposure, respectively.
resultsNebulized sodium nitrite was well tolerated following 6 days of every 8 h administration up to 90 mg, producing significant increases in circulating Hb(Fe)-NO, R-SNO, and FENO. Pulmonary absorption of nitrite was rapid and complete, and plasma exposure dose was proportional through the MTD dosage level of 90 mg, without accumulation following repeated inhalation. At higher dosage levels, DLTs were orthostasis (observed at 120 mg) and hypotension with tachycardia (at 176 mg), but venous methemoglobin did not exceed 3.0 % at any time in any subject. Neither the tolerability nor pharmacokinetics of nitrite was impacted by conditions of mild hypoxia, or co-administration with sildenafil, supporting the safe use of inhaled nitrite in the clinical setting of PAH.
conclusionOn the basis of these results, nebulized sodium nitrite (AIR001) has been advanced into randomized trials in PAH patients.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.