Stereoselective pharmacokinetics of ketamine and norketamine after racemic ketamine or S-ketamine administration during isoflurane anaesthesia in Shetland ponies.

This study investigated the specific behaviors of different forms of ketamine, a common anaesthetic, and its metabolite norketamine, when administered to ponies during anaesthesia with isoflurane. The findings highlighted variations in pharmacokinetics (how the drug behaves inside the body), with significant differences observed in the levels of S-norketamine compared to R-norketamine in the bloodstream.

Research Methodology

• The research involved seven gelding ponies and made use of a crossover study design, which had a 2-month interval.
• A mixture of isoflurane in oxygen was used to induce anaesthesia through a face-mask, and this anaesthesia was maintained according to each pony’s individual minimal alveolar concentration (MAC).
• Either racemic ketamine (a combination of R- and S-ketamine), or S-ketamine alone were administered into the ponies’ right jugular vein.
• Blood samples were taken from the right carotid artery, before and at intervals after ketamine administration, up to 128 minutes.
• The plasma concentrations of ketamine and norketamine enantiomers (mirror-image versions) were measured using capillary electrophoresis.
• Various algorithms and statistical methods were applied to analyse the gathered data for this study.

Findings of the Study

• There were no significant differences in the pharmacokinetics of S- and R-ketamine, whether administered alone or in a racemic mixture.
• The area under the curve (AUC, a measure of drug concentration in the blood over time) and the peak concentration (Cmax) levels for S-norketamine were significantly higher compared to those of R-norketamine in the racemic group.
• Several cardiopulmonary variables including respiratory rate, ventilation volume, carbon dioxide partial pressure, and mean arterial blood pressure were significantly higher in the racemic group, whereas the pulse rate was higher in the S-ketamine group.

Conclusions

• The breakdown products (enantiomers) of ketamine demonstrated different pharmacokinetic profiles after single intravenous administration of racemic ketamine in ponies under anaesthesia.
• The apparent impact of ketamine on cardiopulmonary variables presents an area for further investigation.

This study provides valuable insights into the pharmacokinetics of ketamine and its metabolite norketamine during anesthesia in veterinary medicine. By understanding these dynamics, anesthesiologists can better control and predict the outcomes of ketamine administration, hence improving patient safety and care.