Enantioselective capillary electrophoresis provides insight into the phase II metabolism of ketamine and its metabolites in vivo and in vitro.

Sandbaumhüter, Friederike Andrea; Thormann, Wolfgang (2018). Enantioselective capillary electrophoresis provides insight into the phase II metabolism of ketamine and its metabolites in vivo and in vitro. Electrophoresis, 39(12), pp. 1478-1481. Wiley-VCH 10.1002/elps.201800012

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Glucuronidation catalyzed by uridine-5'-diphospho-glucuronosyl-transferases (UGTs) is the most important reaction in phase II metabolism of drugs and other compounds. O-glucuronidation is more common than N-glucuronidation. The anesthetic, analgesic and antidepressive drug ketamine is metabolized in phase I by cytochrome P450 enzymes to norketamine, hydroxynorketamine (HNK) diastereomers and dehydronorketamine (DHNK). Equine urine samples collected two hours after ketamine injection were treated with β-glucuronidase and analyzed with three enantioselective capillary electrophoresis assays. Concentrations of HNK diastereomers and norketamine were significantly higher in comparison to untreated urine and an increase of ketamine and DHNK levels was found in selected but not all samples. This suggests that O-glucuronides of HNK and N-glucuronides of the other compounds are formed in equines. N-glucuronidation of norketamine was studied in vitro with liver microsomes of different species and the single human enzyme UGT1A4. With equine liver microsomes (ELM) a stereoselective N-glucuronidation of norketamine was found that compares well to the results obtained with urines collected after ketamine administration. No reaction was observed with canine liver microsomes, human liver microsomes and UGT1A4. Incubation of ketamine and DHNK with ELM did not reveal any glucuronidation. Enantioselective CE is suitable to provide insight into the phase II metabolism of ketamine and its metabolites.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Service Sector > Institute for Infectious Diseases > Laboratory for Clinical Pharmacology

UniBE Contributor:

Sandbaumhüter, Friederike Andrea and Thormann, Wolfgang

ISSN:

0173-0835

Publisher:

Wiley-VCH

Language:

English

Submitter:

Wolfgang Thormann

Date Deposited:

28 May 2018 14:48

Last Modified:

28 Oct 2019 23:36

Publisher DOI:

10.1002/elps.201800012

PubMed ID:

29572863

Uncontrolled Keywords:

Capillary electrophoresis Ketamine Metabolism N-glucuronidation O-glucuronidation

BORIS DOI:

10.7892/boris.116599

URI:

https://boris.unibe.ch/id/eprint/116599

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