Early-Phase Postmortem Redistribution of the Enantiomers of Citalopram and Its Demethylated Metabolites in Rats
| Autor: | Henrik Druid, Maria Kingbäck, Björn Carlsson, Fredrik C. Kugelberg |
|---|---|
| Rok vydání: | 2005 |
| Předmět: |
Male
medicine.medical_specialty Time Factors Health Toxicology and Mutagenesis Metabolite Citalopram Toxicology Methylation Postmortem Changes Analytical Chemistry Rats Sprague-Dawley chemistry.chemical_compound Internal medicine Blood drug medicine Animals Environmental Chemistry Tissue Distribution Respiratory system Chemical Health and Safety Lung Chromatography Stereoisomerism Rats medicine.anatomical_structure Endocrinology chemistry Serotonin Reuptake inhibitor Selective Serotonin Reuptake Inhibitors medicine.drug |
| Zdroj: | Journal of Analytical Toxicology. 29:223-228 |
| ISSN: | 1945-2403 0146-4760 |
| Popis: | 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 degrees C vs. 4 degrees 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 degrees 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 degrees 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. |
| Databáze: | OpenAIRE |
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