Stereoselective pharmacokinetics of ketamine and norketamine after constant rate infusion of a subanesthetic dose of racemic ketamine or S-ketamine in Shetland ponies.
Abstract: 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.
Publication Date: 2009-07-02 PubMed ID: 19566468DOI: 10.2460/ajvr.70.7.831Google Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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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.
Cite This Article
APA
Larenza MP, Peterbauer C, Landoni MF, Levionnois OL, Schatzmann U, Spadavecchia C, Thormann W.
(2009).
Stereoselective pharmacokinetics of ketamine and norketamine after constant rate infusion of a subanesthetic dose of racemic ketamine or S-ketamine in Shetland ponies.
Am J Vet Res, 70(7), 831-839.
https://doi.org/10.2460/ajvr.70.7.831 Publication
Researcher Affiliations
- Anesthesiology Section, Department of Clinical Veterinary Medicine, Vetsuisse Faculty, University of Bern, Bern CH-3001, Switzerland.
MeSH Terms
- Animals
- Area Under Curve
- Half-Life
- Horses / metabolism
- Ketamine / administration & dosage
- Ketamine / analogs & derivatives
- Ketamine / blood
- Ketamine / chemistry
- Ketamine / pharmacokinetics
- Male
Citations
This article has been cited 6 times.- Gozalo-Marcilla M, Bettschart-Wolfensberger R, Johnston M, Taylor PM, Redondo JI. Data Collection for the Fourth Multicentre Confidential Enquiry into Perioperative Equine Fatalities (CEPEF4) Study: New Technology and Preliminary Results. Animals (Basel) 2021 Aug 30;11(9).
- Casoni D, Spadavecchia C, Wampfler B, Thormann W, Levionnois OL. Clinical and pharmacokinetic evaluation of S-ketamine for intravenous general anaesthesia in horses undergoing field castration. Acta Vet Scand 2015 May 3;57(1):21.
- Zhao X, Venkata SL, Moaddel R, Luckenbaugh DA, Brutsche NE, Ibrahim L, Zarate CA Jr, Mager DE, Wainer IW. Simultaneous population pharmacokinetic modelling of ketamine and three major metabolites in patients with treatment-resistant bipolar depression. Br J Clin Pharmacol 2012 Aug;74(2):304-14.
- Moaddel R, Venkata SL, Tanga MJ, Bupp JE, Green CE, Iyer L, Furimsky A, Goldberg ME, Torjman MC, Wainer IW. A parallel chiral-achiral liquid chromatographic method for the determination of the stereoisomers of ketamine and ketamine metabolites in the plasma and urine of patients with complex regional pain syndrome. Talanta 2010 Oct 15;82(5):1892-904.
- Medina-Bautista F, Morgaz J, Quirós-Carmona S, Caravaca-Paredes ME, Navarrete-Calvo R, Medina ALS, Gómez-Villamandos R, Granados MDM. Effect of a Constant Rate Infusion of Ketamine on a Variable Rate Infusion of Xylazine in Standing Horses Undergoing Ventriculocordectomy and Laryngoplasty. Vet Sci 2026 Jan 12;13(1).
- Pargätzi G, Bergadano A, Spadavecchia C, Theurillat R, Thormann W, Levionnois OL. Stereoselective Pharmacokinetics of Ketamine Administered at a Low Dose in Awake Dogs. Animals (Basel) 2024 Mar 27;14(7).
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