Trial reportDrug metabolism and disposition: the biological fate of chemicals2010
Characterization of erythrocytic uptake and release and disposition pathways of nitrite, nitrate, methemoglobin, and iron-nitrosyl hemoglobin in the human circulation.
Trial report in Drug metabolism and disposition: the biological fate of chemicals, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
16 citing papers in PubMed, 27 citations in OpenAlex.
- Safety and feasibility of long-term intravenous sodium nitrite infusion in healthy volunteers.PloS one · 2011Trial
- Near-infrared II photobiomodulation augments nitric oxide bioavailability via phosphorylation of endothelial nitric oxide synthase.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2022Article
- Circulating mediators of remote ischemic preconditioning: search for the missing link between non-lethal ischemia and cardioprotection.Oncotarget · 2019Review
- A pilot study on the kinetics of metabolites and microvascular cutaneous effects of nitric oxide inhalation in healthy volunteers.PloS one · 2019Article
- Low dose nitrite improves reoxygenation following renal ischemia in rats.Scientific reports · 2017Article
- Fetal-maternal nitrite exchange in sheep: Experimental data, a computational model and an estimate of placental nitrite permeability.Placenta · 2016Article
- Nitrite modulates bacterial antibiotic susceptibility and biofilm formation in association with airway epithelial cells.Free radical biology & medicine · 2014Article
- Inorganic nitrite supplementation for healthy arterial aging.Journal of applied physiology (Bethesda, Md. : 1985) · 2014Review
- Nitrite reductase activity and inhibition of H₂S biogenesis by human cystathionine ß-synthase.PloS one · 2014Article
- Quantitative Systems Pharmacology Model of NO Metabolome and Methemoglobin Following Long-Term Infusion of Sodium Nitrite in Humans.CPT: pharmacometrics & systems pharmacology · 2013Article
- The identification of nitric oxide as endothelium-derived relaxing factor.Circulation research · 2013Review
- Contribution of intravascular versus interstitial purines and nitric oxide in the regulation of exercise hyperaemia in humans.The Journal of physiology · 2012Review
- Administration of nitrite after chlorine gas exposure prevents lung injury: effect of administration modality.Free radical biology & medicine · 2012Article
- Normoxic cyclic GMP-independent oxidative signaling by nitrite enhances airway epithelial cell proliferation and wound healing.Nitric oxide : biology and chemistry · 2012Article
- Nitric oxide in neurodegeneration: potential benefits of non-steroidal anti-inflammatories.Neuroscience bulletin · 2011Review
- The Effect of Nitric Oxide on Remote Ischemic Preconditioning in Renal Ischemia Reperfusion Injury in Rats.Dose-response : a publication of International Hormesis SocietyArticle
Corrections and comments
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Authors and funding
4 authors at 3 institutions in 1 country.
Funding
Abstract
Nitrite-hemoglobin reactions have been studied extensively in vitro, but there is a lack of information on the kinetics of nitrite and its metabolites in humans. In this study, we developed a nine-compartment physiological pharmacokinetic model to describe the in vivo erythrocytic uptake and release and disposition pathways of nitrite, nitrate, methemoglobin, and iron-nitrosyl hemoglobin in the human circulation. Our model revealed that nitrite entered erythrocytes rapidly with a rate constant of 0.256 min(-1) (i.e., half-life = 2.71 min). The formation of iron-nitrosyl hemoglobin from nitrite, which involves the reduction of nitrite by deoxyhemoglobin to generate nitric oxide (NO) and reaction of NO with deoxyhemoglobin to form iron-nitrosyl hemoglobin, occurred rapidly as well (k = 2.02 min(-1); half-life = 0.343 min = 21 s). The disposition kinetics of methemoglobin was complex. Nitrate formation occurred primarily in erythrocytes through the nitrite-oxyhemoglobin reaction and was higher when nitrite was administered intra-arterially than intravenously. Nitrate reduction was an insignificant metabolic pathway. This study is the first to comprehensively evaluate the kinetics of nitrite and its metabolites in humans and provides unique insights into the rapid equilibrium of nitrite into erythrocytes and conversion to NO in the red cell, which is kinetically associated with vasodilation.
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Registered trials
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.