ISSN:
0887-6134
Keywords:
Chemistry
;
Analytical Chemistry and Spectroscopy
Source:
Wiley InterScience Backfile Collection 1832-2000
Topics:
Chemistry and Pharmacology
Notes:
In order to determine the fraction of an intravenous bolus dose of ketamine which is metabolized in vivo to the corresponding N-desmethyl compound, norketamine, a novel stable isotope technique was developed and applied to a study in rats. Co-injection of equimoiar amounts of deuterium-labeled ketamine and unlabeled norketamine to four animals, followed by gas chromatographic/mass spectrometric analysis of both the administered compounds and deuterium-labeled norketamine in plasma yielded pharmacokinetic data from which the fraction of the parent drug subjected to N-demethylation (fm) was calculated from AUC data to be 36.8 ± 2.4%. It is concluded that this stable isotope co-administration technique represents a powerful approach to the determination of fm, in that the pharmacokinetics of the metabolite of interest, given as the preformed compound and generated in vivo, are determined simultaneously. This experimental design thus obviates the influence of time-dependent changes in metabolite clearance which may complicate the interpretation of studies performed using the classical cross-over design.
Additional Material:
2 Ill.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1002/bms.1200180607
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