Pharmacokinetics of dextromethorphan and its metabolites in horses following a single oral administration.

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.