Pharmacokinetics of dextromethorphan and its metabolites in horses following a single oral administration.
Abstract: Dextromethorphan is an N-methyl-D-aspartate (NMDA) non-competitive antagonist commonly used in human medicine as an antitussive. Dextromethorphan is metabolized in humans by cytochrome P450 2D6 into dextrorphan, which is reported to be more potent than the parent compound. The goal of this study is to describe the metabolism of and determine the pharmacokinetics of dextromethorphan and its major metabolites following oral administration to horses. A total of 23 horses received a single oral dose of 2 mg/kg. Blood samples were collected at time 0 and at various times up to 96 h post drug administration. Urine samples were collected from 12 horses up to 120 h post administration. Plasma and urine samples were analyzed using liquid chromatography-mass spectrometry, and the resulting data analyzed using non-compartmental analysis. The C , T , and the t of dextromethorphan were 519.4 ng/mL, 0.55 h, and 12.4 h respectively. The area under the curve of dextromethorphan, free dextrorphan, and conjugated dextrorphan were 563.8, 2.19, and 6,691 h*ng/mL respectively. In addition to free and glucuronidated dextrorphan, several additional glucuronide metabolites were identified in plasma, including hydroxyl-desmethyl dextrorphan, desmethyl dextrorphan, and three forms of hydroxylated dextrorphan. Dextromethorphan was found to be eliminated from the urine predominately as the O-demethylated metabolite, dextrorphan. Several additional metabolites including several novel hydroxy-dextrorphan metabolites were also detected in the urine in both free and glucuronidated forms. No significant undesirable behavioural effects were noted throughout the duration of the study. Copyright © 2016 John Wiley & Sons, Ltd.
Copyright © 2016 John Wiley & Sons, Ltd.
Publication Date: 2016-10-03 PubMed ID: 27580591DOI: 10.1002/dta.2060Google Scholar: Lookup The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
- Journal Article
Summary
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The research article investigates how dextromethorphan, a common human antitussive, is metabolized in horses following a one-off oral run. It also tracks the pharmacokinetics of dextromethorphan and its primary metabolites to observe how these substances are processed and expelled by the horses’ systems.
Research Methodology
- To carry out the study, a total of 23 horses were given a single oral dose of 2mg/kg of dextromethorphan.
- Blood samples from these horses were taken at various intervals for up to 96 hours after they took the drug. This was done to track the drug’s concentrations over time.
- Moreover, the researchers also collected urine samples from 12 horses for up to 120 hours after the drug was administered.
- The blood and urine samples were then subjected to liquid chromatography-mass spectrometry to detect and quantify the dextromethorphan and its metabolites.
- The collected data were then examined using non-compartmental analysis. This type of analysis is used to measure pharmacokinetics, the biochemical process of drug distribution within the body, without making assumptions about the compartments.
Results of the Study
- The peak concentration (C) and the time it took to reach the peak concentration (T) for dextromethorphan were 519.4 ng/mL, and 0.55 hours, respectively. Its elimination half-life (t), the time it took for the concentration to decrease to half, was recorded as 12.4 hours.
- There are two major forms of the metabolite dextrorphan (Free and Conjugated), both of which were less abundant in comparison with the parent compound. Free dextrorphan had an area under the curve (a measure of drug exposure over time) of 2.19 h*ng/mL, while for conjugated dextrorphan, it was 6691 h*ng/mL.
- Apart from these two, various other glucuronide metabolites, including hydroxyl-desmethyl dextrorphan, desmethyl dextrorphan, and three forms of hydroxylated dextrorphan, were identified in plasma.
- In urine, dextromethorphan was let out mostly as the O-demethylated metabolite, dextrorphan. In addition to this, there were also some other metabolites, including several unique hydroxy-dextrorphan metabolites, found in both free and glucuronidated forms.
- The test didn’t lead to any appreciable undesirable behavioural effects in the horses throughout the duration of the study.
Cite This Article
APA
Corado CR, McKemie DS, Knych HK.
(2016).
Pharmacokinetics of dextromethorphan and its metabolites in horses following a single oral administration.
Drug Test Anal, 9(6), 880-887.
https://doi.org/10.1002/dta.2060 Publication
Researcher Affiliations
- K.L. Maddy Analytical Chemistry Laboratory, School of Veterinary Medicine, University of California, Davis, CA, 95620, USA.
- K.L. Maddy Analytical Chemistry Laboratory, School of Veterinary Medicine, University of California, Davis, CA, 95620, USA.
- K.L. Maddy Analytical Chemistry Laboratory, School of Veterinary Medicine, University of California, Davis, CA, 95620, USA.
- Department of Veterinary Molecular Biosciences, School of Veterinary Medicine, University of California, Davis, CA, 95620, USA.
MeSH Terms
- Administration, Oral
- Animals
- Antitussive Agents / administration & dosage
- Antitussive Agents / blood
- Antitussive Agents / metabolism
- Antitussive Agents / urine
- Chromatography, Liquid / methods
- Dextromethorphan / administration & dosage
- Dextromethorphan / blood
- Dextromethorphan / metabolism
- Dextromethorphan / urine
- Dextrorphan / blood
- Dextrorphan / metabolism
- Dextrorphan / urine
- Drug Monitoring / methods
- Excitatory Amino Acid Antagonists / administration & dosage
- Excitatory Amino Acid Antagonists / blood
- Excitatory Amino Acid Antagonists / metabolism
- Excitatory Amino Acid Antagonists / urine
- Female
- Glucuronides / blood
- Glucuronides / metabolism
- Glucuronides / urine
- Horses / blood
- Horses / metabolism
- Horses / urine
- Male
- Mass Spectrometry / methods
Citations
This article has been cited 2 times.- Gretler SR, Finno CJ, McKemie DS, Kass PH, Knych HK. Metabolism, pharmacokinetics and selected pharmacodynamic effects of codeine following a single oral administration to horses. Vet Anaesth Analg 2020 Sep;47(5):694-704.
- Foti Randazzese S, Toscano F, Gambadauro A, La Rocca M, Altavilla G, Carlino M, Caminiti L, Ruggeri P, Manti S. Neuromodulators in Acute and Chronic Cough in Children: An Update from the Literature. Int J Mol Sci 2024 Oct 18;25(20).
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