Nitrite and nitrate pharmacokinetics in the dog, sheep, and pony.
Abstract: Elimination kinetics of nitrite and nitrate in the dog, sheep, and pony were determined. The elimination half-lives of nitrite were 0.499, 0.475, and 0.566 hours in the dog, sheep, and pony, respectively; those of nitrate were 44.681, 4.233, and 4.821 hours. Apparent specific volumes of distribution (V'd) of nitrite were variable among the 3 species--1,623.7 ml/kg in the dog, 278.0 ml/kg in the sheep, and 191.6 ml/kg in the pony. The V'd of nitrate were less varied--dog, 238.5 ml/kg; sheep, 291.1 ml/kg; and pony, 209.3 ml/kg. In the in vitro studies on protein binding in canine plasma, the extent of nitrite-protein binding varied directly with concentrations of 5 to 25 mug of NO2 minus/ml (4.5 to 13.6% bound), but inversely with concentrations of 50 to 100 mug of NO2 minus/ml (9.8 to 8.8% bound). Less than 1% of nitrate was bound to canine plasma at equimolar concentrations (5 to 100 mug of NO3 minus/ml).
Publication Date: 1975-07-01 PubMed ID: 1147360
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- Journal Article
- Research Support
- U.S. Gov't
- P.H.S.
Summary
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The research investigated how nitrite and nitrate are eliminated from the bodies of dogs, sheep, and ponies. Differences among the three species were highlighted and the relative impact of these substances on plasma protein binding was explored.
Elimination Kinetics and Half-Lives
- This study observed the elimination kinetics, which essentially is the rate of removal of nitrite and nitrate from the body, in dogs, sheep, and ponies.
- Half-lives refer to the period it takes for a substance to reduce to half its initial amount. Here, nitrite had half-lives of 0.499 hours in the dog, 0.475 hours in the sheep, and 0.566 hours in the pony.
- For nitrate, these were significantly longer – 44.681 hours for dogs and similar times of around 4.23 to 4.82 hours for sheep and ponies.
Volumes of Distribution
- The volume of distribution (V’d) is a theoretical value that indicates the apparent space in the body available to contain the drug. It helps determine dosing levels for medications.
- The volumes of distribution for both nitrite and nitrate varied among the three species.
- For nitrite, these were 1,623.7 ml/kg in the dog, 278.0 ml/kg in the sheep, and 191.6 ml/kg in the pony.
- For nitrate, the volumes were comparably lower and less varied: 238.5 ml/kg in the dog, 291.1 ml/kg in the sheep, and 209.3 ml/kg in the pony.
In Vitro Studies on Protein Binding in Canine Plasma
- The study also extended to examine how nitrite and nitrate bind with proteins in canine plasma in a controlled environment (in vitro). This protein binding influences how the substance is distributed within the body.
- Interestingly, the extent of nitrite-protein binding within canine plasma was found to increase with nitrite concentrations between 5 and 25 micrograms of NO2-/ml but decrease between 50 to 100 micrograms of NO2-/ml. In other words, at lesser concentrations, more nitrite binds to proteins, but at higher concentrations, fewer nitrites are bound.
- For nitrate, it was found that less than 1% of it bound to canine plasma proteins at equal concentrations ranging between 5 to 100 micrograms of NO3-/ml. This marks a notable difference between the binding tendencies of nitrite and nitrate to plasma proteins.
Cite This Article
APA
Schneider NR, Yeary RA.
(1975).
Nitrite and nitrate pharmacokinetics in the dog, sheep, and pony.
Am J Vet Res, 36(7), 941-947.
Publication
Researcher Affiliations
MeSH Terms
- Animals
- Dog Diseases / blood
- Dogs / blood
- Half-Life
- Horse Diseases / blood
- Horses / blood
- Injections, Intravenous
- Kinetics
- Methemoglobinemia / veterinary
- Nitrates / blood
- Nitrites / administration & dosage
- Nitrites / blood
- Protein Binding
- Sheep / blood
- Sheep Diseases / blood
- Time Factors
Citations
This article has been cited 6 times.- Schrenk D, Bignami M, Bodin L, Chipman JK, Del Mazo J, Grasl-Kraupp B, Hoogenboom LR, Leblanc JC, Nebbia CS, Nielsen E, Ntzani E, Petersen A, Sand S, Schwerdtle T, Vleminckx C, Wallace H, Bampidis V, Cottrill B, Frutos MJ, Furst P, Parker A, Binaglia M, Christodoulidou A, Gergelova P, Guajardo IM, Wenger C, Hogstrand C. Risk assessment of nitrate and nitrite in feed.. EFSA J 2020 Nov;18(11):e06290.
- Hon YY, Lin EE, Tian X, Yang Y, Sun H, Swenson ER, Taveira-Dasilva AM, Gladwin MT, Machado RF. Increased consumption and vasodilatory effect of nitrite during exercise.. Am J Physiol Lung Cell Mol Physiol 2016 Feb 15;310(4):L354-64.
- Dayal B, Ertel NH. Studies on N-nitroso bile acid amides in relation to their possible role in gastrointestinal cancer.. Lipids 1997 Dec;32(12):1331-40.
- Imaizumi K, Tyuma I, Imai K, Kosaka H, Ueda Y. In vivo studies on methemoglobin formation by sodium nitrite.. Int Arch Occup Environ Health 1980 Feb;45(2):97-104.
- Yoshida K, Kasama K. Biotransformation of nitric oxide.. Environ Health Perspect 1987 Aug;73:201-5.
- Grudziński I, Szymański A, Chomiczewski K. The effect of exercise associated with subchronic poisoning with potassium nitrate and sodium nitrite on the processes of intestinal absorption of D-xylose in rats.. Arch Environ Contam Toxicol 1991 Sep;21(3):462-7.
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