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Home / Equine Research Bank / J Vet Pharmacol Ther / Stereoselective biotransformation of ketamine in equine live...
Journal of veterinary pharmacology and therapeutics2008; 31(5); 446-455; doi: 10.1111/j.1365-2885.2008.00972.x

Stereoselective biotransformation of ketamine in equine liver and lung microsomes.

Abstract: Stereoselectivity has to be considered for pharmacodynamic and pharmacokinetic features of ketamine. Stereoselective biotransformation of ketamine was investigated in equine microsomes in vitro. Concentration curves were constructed over time, and enzyme activity was determined for different substrate concentrations using equine liver and lung microsomes. The concentrations of R/S-ketamine and R/S-norketamine were determined by enantioselective capillary electrophoresis. A two-phase model based on Hill kinetics was used to analyze the biotransformation of R/S-ketamine into R/S-norketamine and, in a second step, into R/S-downstream metabolites. In liver and lung microsomes, levels of R-ketamine exceeded those of S-ketamine at all time points and S-norketamine exceeded R-norketamine at time points below the maximum concentration. In liver and lung microsomes, significant differences in the enzyme velocity (V(max)) were observed between S- and R-norketamine formation and between V(max) of S-norketamine formation when S-ketamine was compared to S-ketamine of the racemate. Our investigations in microsomal reactions in vitro suggest that stereoselective ketamine biotransformation in horses occurs in the liver and the lung with a slower elimination of S-ketamine in the presence of R-ketamine. Scaling of the in vitro parameters to liver and lung organ clearances provided an excellent fit with previously published in vivo data and confirmed a lung first-pass effect.
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Publication Date: 2008-11-13 PubMed ID: 19000264PubMed Central: PMC2821671DOI: 10.1111/j.1365-2885.2008.00972.xGoogle Scholar: Lookup
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Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

The research investigated the varying rates at which a drug called ketamine is metabolically processed in horse liver and lung cells. The researchers found that the rate differed based on the structural variant of the drug and the organ in which it was processed, revealing new insights into how ketamine behaves in the body of horses.

Study context

  • Ketamine is a medication with multiple uses such as in anesthesia and pain management. It exists in two structural forms, referred to as R and S stereoisomers.
  • These stereoisomers can sometimes be metabolized differently in the body, due to their distinct 3D structures- a phenomenon known as stereoselective biotransformation.
  • This research aimed to investigate the stereoselective biotransformation of ketamine in horse liver and lung cells, as previous research has suggested that varying rates of metabolism could occur in different organs.

Methodology

  • The researchers conducted the study in vitro, meaning they performed the experiments using cells in a controlled environment outside of a living organism.
  • They used horse liver and lung cells, also known as microsomes, to test how they metabolized R and S ketamine.
  • The concentrations of the stereoisomers and their metabolites were measured over time using a method called enantioselective capillary electrophoresis.
  • The researchers used a two-phase model based on Hill kinetics to analyze the data.

Findings

  • The researchers found that both in liver and lung cells, the concentration of R-ketamine was higher than that of S-ketamine at all tested time points. Conversely, the concentration of S-norketamine, a metabolite of ketamine, was higher than that of R-norketamine at times below the maximum concentration.
  • The metabolism rate, or enzyme velocity, differed significantly between the formation of S- and R-norketamine and between the maximum enzyme velocities when comparing S-ketamine with the racemic mix of both forms.
  • This shows that stereo-selective biotransformation of ketamine indeed occurs in horses and it is more pronounced in the liver and the lung.

Significance of the study

  • This research provides important information on how ketamine is processed in the body of horses, which can guide dosing and administration decisions in veterinary medicine.
  • The findings confirm that the lungs carry out a ‘first-pass effect’, metabolizing a substantial amount of the drug before it reaches systemic circulation.
  • The study also shows how in vitro experiments can be successfully correlated with in vivo conditions, providing further confidence in the use of in vitro studies.

Cite This Article

APA
Schmitz A, Portier CJ, Thormann W, Theurillat R, Mevissen M. (2008). Stereoselective biotransformation of ketamine in equine liver and lung microsomes. J Vet Pharmacol Ther, 31(5), 446-455. https://doi.org/10.1111/j.1365-2885.2008.00972.x

Publication

Journal of veterinary pharmacology and therapeutics
ISSN: 1365-2885
NlmUniqueID: 7910920
Country: England
Language: English
Volume: 31
Issue: 5
Pages: 446-455

Researcher Affiliations

Schmitz, A
  • Division of Veterinary Pharmacology and Toxicology, Vetsuisse Faculty, University of Bern, Bern, Switzerland.
Portier, C J
    Thormann, W
      Theurillat, R
        Mevissen, M

          MeSH Terms

          • Analgesics / metabolism
          • Analgesics / pharmacokinetics
          • Animals
          • Biotransformation
          • Female
          • Horses
          • In Vitro Techniques
          • Ketamine / analogs & derivatives
          • Ketamine / metabolism
          • Ketamine / pharmacokinetics
          • Lung / metabolism
          • Male
          • Metabolic Clearance Rate
          • Microsomes, Liver / metabolism
          • Models, Biological
          • Receptors, N-Methyl-D-Aspartate / antagonists & inhibitors
          • Stereoisomerism
          • Substrate Specificity

          Grant Funding

          • Z01 ES048002-21 / Intramural NIH HHS

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