| 1. |
- Holmgren, Per, et al.
(författare)
-
Enantioselective analysis of citalopram and its metabolites in postmortem blood and genotyping for CYD2D6 and CYP2C19
- 2004
-
Ingår i: Journal of Analytical Toxicology. - : Oxford University Press (OUP). - 0146-4760 .- 1945-2403. ; 28:2, s. 94-104
-
Tidskriftsartikel (refereegranskat)abstract
- Citalopram, a selective serotonin reuptake inhibitor, is one of the most commonly found drugs in Swedish forensic autopsy cases. Citalopram is a racemic drug with 50:50 of the S- and R- enantiomers. Enantioselective analysis of citalopram and its metabolites desmethylcitalopram and didesmethylcitalopram were performed in femoral blood from 53 autopsy cases by a chiral high-performance liquid chromatography (HPLC) method. The mean (± standard deviation) S/R ratio for citalopram was 0.67 ± 0.25 and for desmethylcitalopram, 0.68 ± 0.20. We found increasing S/R ratios with increasing concentrations of citalopram. We also found that high citalopram S/R ratios were associated with a high parent drug-to-metabolite ratio and may be an indicator of recent intake. Citalopram is metabolized by cytochrome P450 (CYP) 3A4, 2C19, and 2D6. Genotyping for the polymorphic CYP2C19 and CYP2D6 revealed no poor metabolizers regarding CYP2C19 and only 2 (3.8%) poor metabolizers regarding CYP2D6. The presence of drugs metabolized by and/or inhibiting these enzymes in several of the cases suggests that such pharmacokinetic interactions are a more important (practical) problem than metabolic deficiency. Enantioselective analysis of citalopram and its metabolites can provide additional information when interpreting forensic toxicology results and might be a necessity in the future.
|
|
| 2. |
- Holmgren, Per, et al.
(författare)
-
Stability of drugs in stored postmortem femoral blood and vitreous humor
- 2004
-
Ingår i: Journal of Forensic Sciences. - 0022-1198 .- 1556-4029. ; 49:4, s. 820-825
-
Tidskriftsartikel (refereegranskat)abstract
- The stability of 46 drugs in postmortem femoral blood stored for one year at -20°C was investigated. The drugs included benzodiazepines, antidepressants, analgetics and hypnotics. For seven drugs we found a significant change in the concentration between the first and second analysis. Five substances; ethanol, desmethylmianserin, 7-amino-nitrazepam, THC and zopiclone showed a decrease in the concentration whereas the concentrations of two substances; ketobemidone and thioridazine increased. However, the changes observed were not of such an order that it would affect the interpretation in normal forensic casework. We also investigated the possible influence of potassium fluoride on the concentrations of the 46 drugs in vitreous humor after storage for one year. For two substances, ethanol and zopiclone, there were significantly lower concentrations in the samples without potassium fluoride. Furthermore, we also studied the correlation between the concentrations in femoral blood and vitreous humor. For 23 substances there was a significant difference between the concentrations in the vitreous humor and femoral blood. Significant correlations between the concentrations in these two specimens were found for 23 substances, indicating that vitreous humor can be an alternative specimen when blood samples are not available, provided that such correlation exists for the particular substance. Statistical analysis also revealed a correlation between the degree of protein binding of the different drugs and percentage of vitreous/femoral blood concentrations.
|
|
| 3. |
- Kugelberg, Fredrik, 1974-, et al.
(författare)
-
Postmortem redistribution of the enantiomers of citalopram and its metabolites : an experimental study in rats
- 2004
-
Ingår i: Journal of Analytical Toxicology. - : Oxford University Press (OUP). - 0146-4760 .- 1945-2403. ; 28:8, s. 631-637
-
Tidskriftsartikel (refereegranskat)abstract
- A rat model was used to study if postmortem redistribution of the S- and R-enantiomers of citalopram (CIT) and its metabolites demethylcitalopram (DCIT) and didemethylcitalopram (DDCIT) occurs after three different subcutaneous dosing procedures with racemic CIT. Two groups underwent chronic administration (20 mg/kg daily) using osmotic pumps. After 10 days, 1 of these groups received an acute-on-chronic drug challenge with a single injection of 100 mg/kg. The third group received the single 100 mg/kg dose only. Heart blood and brain samples were collected antemortem and 1, 3, or 24 h postmortem for enantioselective HPLC analysis. Increased postmortem blood drug and metabolite concentrations compared with corresponding antemortem concentrations were observed in all groups (p < 0.05 to p < 0.001). At 24 h after death, the ratios between postmortem and antemortem blood concentrations were around 3–4 for CIT as well as for the metabolites. In the brain, no major differences between antemortem and postmortem drug and metabolite concentrations were observed. The enantiomeric (S/R) concentrations ratios of CIT and metabolites in blood and brain were of similar magnitude before and after death. No differences between antemortem and postmortem parent drug-to-metabolite (P/M) ratios for CIT/DCIT in blood were observed. Finally, this animal model demonstrates that the S- and R-enantiomers of CIT and its metabolites were redistributed to the same extent postmortem.
|
|
