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Pharmacokinetics of dextromethorphan and its metabolites in horses following a single oral administration.
- Source :
-
Drug testing and analysis [Drug Test Anal] 2017 Jun; Vol. 9 (6), pp. 880-887. Date of Electronic Publication: 2016 Oct 03. - Publication Year :
- 2017
-
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 <subscript>max</subscript> , T <subscript>max</subscript> , and the t <subscript>1/2</subscript> 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.<br /> (Copyright © 2016 John Wiley & Sons, Ltd.)
- Subjects :
- Administration, Oral
Animals
Antitussive Agents administration & dosage
Antitussive Agents blood
Antitussive Agents metabolism
Antitussive Agents urine
Chromatography, Liquid methods
Dextromethorphan administration & dosage
Dextromethorphan metabolism
Dextrorphan blood
Dextrorphan metabolism
Dextrorphan urine
Drug Monitoring methods
Excitatory Amino Acid Antagonists administration & dosage
Excitatory Amino Acid Antagonists metabolism
Female
Glucuronides blood
Glucuronides metabolism
Glucuronides urine
Horses metabolism
Male
Mass Spectrometry methods
Dextromethorphan blood
Dextromethorphan urine
Excitatory Amino Acid Antagonists blood
Excitatory Amino Acid Antagonists urine
Horses blood
Horses urine
Subjects
Details
- Language :
- English
- ISSN :
- 1942-7611
- Volume :
- 9
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Drug testing and analysis
- Publication Type :
- Academic Journal
- Accession number :
- 27580591
- Full Text :
- https://doi.org/10.1002/dta.2060