Enantioselective N-demethylation of ketamine in the horse.

This research investigates the enantioselective N-demethylation of Ketamine in horses. The study involves administering Ketamine to four healthy horses and studying the resulting metabolic activity, focusing particularly on enantioselectivity in the metabolic reaction.

Purpose of the Research

• The research aims to investigate the potential enantioselectivity of the main metabolic reaction, specifically N-demethylation, of ketamine (KTM) in horses.

Ketamine (KTM) and Its Characteristics

• Ketamine is a dissociative anaesthetic drug widely used in both humans and animals.
• KTM, being a chiral compound, has two enantiomers: R(-) KTM and S(+) KTM.
• The commercial drug form is a racemic mixture of these two enantiomers.

Research Details

• The research was conducted on four healthy, cross-bred male horses.
• For surgical purposes, they were dosed intravenously with a single dose of 6.0 mg rac-KTM per kg.
• Blood samples were taken at various intervals – 2, 5, 10, 20, and 40 minutes – after the dosage was administered.
• The blood samples were then processed and prepared for analysis.

Analysis Process

• Plasma from the blood samples was extracted and adjusted to a specific pH before being exposed to diethyl ether and evaporated.
• The residue was dissolved and then adsorbed onto specific cassettes for further analysis using an automated sample processor.
• The analytes were then eluted and chromatographed on a C18 column, with specific retention times recorded for Nor KTM and KTM.
• The fractions were collected and re-extracted, proceeded by further evaporation to dryness.
• The purified residue was then dissolved and chromatographed under specific conditions.
• This allowed for the determination of plasma concentration over time of unchanged KTM and its main metabolite, Nor KTM.

Results

• The concentration versus time profile of ketamine and its main metabolite was found to be very similar to previously published profiles for horses, dogs, and ruminants.