Stereoselective pharmacokinetics of ketamine and norketamine after constant rate infusion of a subanesthetic dose of racemic ketamine or S-ketamine in Shetland ponies.

The research article describes a study in which the pharmacokinetics of ketamine and norketamine are evaluated in Shetland ponies. It concludes that the use of S-ketamine in constant rate infusion (CRI) might be preferred over racemic ketamine due to faster elimination.

Methods and Study Structure

• The research was set up as a crossover study involving five 6-year-old Shetland pony geldings. These ponies weighed between 101 and 152 kg.
• Each pony underwent a constant rate infusion (CRI) of both racemic ketamine and S-ketamine, with a one-month interval between treatments.
• The specific dosages for each substance were: racemic ketamine – loading dose of 0.6 mg/kg and CRI of 0.02 mg/kg/min; S-ketamine – loading dose of 0.3 mg/kg and CRI of 0.01 mg/kg/min.

Sample Collection and Analysis

• Arterial blood samples were collected before the start of drug administration and at various points during and post-administration.
• The concentrations of ketamine and norketamine enantiomers were quantified using capillary electrophoresis. The concentrations were then plotted against time to create curves, which were analyzed using a monocompartmental model.
• The plasma disposition curves for R-norketamine and S-norketamine were clarified by measuring the area under the concentration versus time curve (AUC), the maximum concentration (Cmax), and the time until Cmax.

Research Findings

• The results demonstrated a faster decrease in plasma concentrations of S-ketamine and a faster increase in its biodegradation products after S-ketamine CRI compared to the results after racemic ketamine CRI.
• The R-norketamine was also eliminated more quickly compared to S-norketamine.
• Significant differences were seen between treatments for the AUC of S-ketamine and within the racemic ketamine CRI for AUC and Cmax of norketamine isomers.

Conclusions

• The study concludes that constant rate infusion of S-ketamine may be preferable over racemic ketamine for standing equids. This is primarily because the S-enantiomer was eliminated faster when infused alone, rather than being part of a racemic mixture.