Enantioselective CE analysis of hepatic ketamine metabolism in different species in vitro

Schmitz, Andrea; Thormann, Wolfgang; Moessner, Lone; Theurillat, Regula; Helmja, Kati; Mevissen, Meike (2010). Enantioselective CE analysis of hepatic ketamine metabolism in different species in vitro. Electrophoresis, 31(9), pp. 1506-16. Weinheim: Wiley-VCH 10.1002/elps.200900703

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Ketamine, an injectable anesthetic and analgesic consisting of a racemic mixture of S-and R-ketamine, is routinely used in veterinary and human medicine. Nevertheless, metabolism and pharmacokinetics of ketamine have not been characterized sufficiently in most animal species. An enantioselective CE assay for ketamine and its metabolites in microsomal preparations is described. Racemic ketamine was incubated with pooled microsomes from humans, horses and dogs over a 3 h time interval with frequent sample collection. CE data revealed that ketamine is metabolized enantioselectively to norketamine (NK), dehydronorketamine and three hydroxylated NK metabolites in all three species. The metabolic patterns formed differ in production rates of the metabolites and in stereoselectivity of the hydroxylated NK metabolites. In vitro pharmacokinetics of ketamine N-demethylation were established by incubating ten different concentrations of racemic ketamine and the single enantiomers of ketamine for 8 min and data modeling was based on Michaelis-Menten kinetics. These data revealed a reduced intrinsic clearance of the S-enantiomer in the racemic mixture compared with the single S-enantiomer in human microsomes, no difference in equine microsomes and the opposite effect in canine microsomes. The findings indicate species differences with possible relevance for the use of single S-ketamine versus racemic ketamine in the clinic.

Item Type:

Journal Article (Original Article)

Division/Institute:

05 Veterinary Medicine > Department of Clinical Research and Veterinary Public Health (DCR-VPH) > Veterinary Pharmacology and Toxicology
04 Faculty of Medicine > Service Sector > Institute of Clinical Pharmacology and Visceral Research [discontinued]

UniBE Contributor:

Schmitz, Andrea; Thormann, Wolfgang; Mössner, Lone and Mevissen, Meike

ISSN:

0173-0835

Publisher:

Wiley-VCH

Language:

English

Submitter:

Factscience Import

Date Deposited:

04 Oct 2013 14:11

Last Modified:

04 May 2014 23:05

Publisher DOI:

10.1002/elps.200900703

PubMed ID:

20358543

Web of Science ID:

000277844500012

URI:

https://boris.unibe.ch/id/eprint/1729 (FactScience: 203669)

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