Stereoselective pharmacokinetics of ketamine and norketamine after constant rate infusion of a subanesthetic dose of racemic ketamine or S-ketamine in Shetland ponies.
OBJECTIVE
To evaluate pharmacokinetics of ketamine and norketamine enantiomers after constant rate infusion (CRI) of a subanesthetic dose of racemic ketamine or S-ketamine in ponies.


METHODS
Five 6-year-old Shetland pony geldings that weighed between 101 and 152 kg.


METHODS
In a crossover study, each pony received a CRI of racemic ketamine (loading dose, 0.6 mg/kg; CRI, 0.02 mg/kg/min) and S-ketamine (loading dose, 0.3 mg/kg; CRI, 0.01 mg/kg/min), with a 1-month interval between treatments. Arterial blood samples were collected before and at 5, 15, 30, 45, and 60 minutes during drug administration and at 5, 10, 30, and 60 minutes after discontinuing the CRI. Plasma ketamine and norketamine enantiomers were quantified by use of capillary electrophoresis. Individual R-ketamine and S-ketamine concentration-versus-time curves were analyzed by use of a monocompartmental model. Plasma disposition curves for R-norketamine and S-norketamine were described by estimating the area under the concentration-versus-time curve (AUC), maximum concentration (Cmax), and time until Cmax.


RESULTS
Plasma concentrations of S-ketamine decreased and biodegradation products increased more rapidly after S-ketamine CRI, compared with results after racemic ketamine CRI. The R-norketamine was eliminated faster than was the S-norketamine. Significant differences between treatments were found for the AUC of S-ketamine and within the racemic ketamine CRI for the AUC and Cmax of norketamine isomers.


CONCLUSIONS
CRI of S-ketamine may be preferable over CRI of racemic ketamine in standing equids because the S-enantiomer was eliminated faster when infused alone instead of as part of a racemic mixture.
Larenza
M Paula
MP
Anesthesiology Section, Department of Clinical Veterinary Medicine, Vetsuisse Faculty, University of Bern, Bern CH-3001, Switzerland.
Peterbauer
Christoph
C
Landoni
M Fabiana
MF
Levionnois
Olivier L
OL
Schatzmann
Urs
U
Spadavecchia
Claudia
C
Thormann
Wolfgang
W
D000818:Animals; D019540:Area Under Curve; D006207:Half-Life; D006736:Horses / Q000378:metabolism*; D007649:Ketamine / Q000008:administration & dosage* / Q000031:analogs & derivatives* / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D008297:Male
D007649:Ketamine; C033419:norketamine