Stereoselective biotransformation of ketamine in equine liver and lung microsomes

Schmitz, A; Portier, C J; Thormann, W; Theurillat, R; Mevissen, Meike (2008). Stereoselective biotransformation of ketamine in equine liver and lung microsomes. Journal of veterinary pharmacology and therapeutics, 31(5), pp. 446-55. Oxford: Blackwell Scientific Publications 10.1111/j.1365-2885.2008.00972.x

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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.

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, Theurillat, Regula, Mevissen, Meike
Subjects:	600 Technology > 630 Agriculture
ISSN:	0140-7783
ISBN:	19000264
Publisher:	Blackwell Scientific Publications
Submitter:	Factscience Import
Date Deposited:	04 Oct 2013 15:05
Last Modified:	05 Dec 2022 14:20
Publisher DOI:	10.1111/j.1365-2885.2008.00972.x
PubMed ID:	19000264
Web of Science ID:	000259682300008
URI:	https://boris.unibe.ch/id/eprint/28341 (FactScience: 120161)