Journal Article

Early-Phase Postmortem Redistribution of the Enantiomers of Citalopram and Its Demethylated Metabolites in Rats

Fredrik C. Kugelberg, Maria Kingbäck, Björn Carlsson and Henrik Druid

in Journal of Analytical Toxicology

Volume 29, issue 4, pages 223-228
Published in print May 2005 | ISSN: 0146-4760
Published online May 2005 | e-ISSN: 1945-2403 | DOI: http://dx.doi.org/10.1093/jat/29.4.223
Early-Phase Postmortem Redistribution of the Enantiomers of Citalopram and Its Demethylated Metabolites in Rats

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The aim of this study was to investigate the early-phase postmortem redistribution of the enantiomers of citalopram (CIT) and its metabolites demethylcitalopram (DCIT) and didemethylcitalopram (DDCIT) in a rat model. Furthermore, we wanted to examine the role of the lungs as a reservoir of postmortem drug release and to investigate the influence of storage temperature (21 °C vs. 4°C) on postmortem changes. Rats were administered a single CIT dose of 100 mg/kg (s.c.), and heart blood and lung samples were collected antemortem and 15 min postmortem for enantioselective high-performance liquid chromatographic analysis. About three times higher blood drug and metabolite levels were observed in the postmortem rats than in the antemortem rats (p < 0.0001). Refrigeration at 4°C did not prevent, but significantly reduced, the postmortem increase in heart blood CIT levels as compared to the concentrations in the rats stored at 21°C (p < 0.05). The lung drug concentrations were lower postmortem than antemortem (p < 0.05). The enantiomeric (S/R) concentration ratios of CIT and metabolites in blood and lungs were of similar magnitude before and after death. The parent-drug-to-metabolite ratios for CIT/DCIT were unchanged after death. In conclusion, this study shows that heart blood CIT and metabolite levels increase rapidly after death. Further, a fall in postmortem CIT concentrations in the lungs was observed, indicating that the lungs seemed to represent one major source of drug release during early-phase postmortem redistribution.

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Subjects: Medical Toxicology ; Toxicology (Non-medical)

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