Postmortem redistribution of the enantiomers of citalopram and its metabolites: an experimental study in rats

J Anal Toxicol. 2004 Nov-Dec;28(8):631-7. doi: 10.1093/jat/28.8.631.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Citalopram / administration & dosage
  • Citalopram / pharmacokinetics*
  • Dose-Response Relationship, Drug
  • Infusion Pumps, Implantable
  • Injections, Subcutaneous
  • Male
  • Osmosis
  • Postmortem Changes*
  • Rats
  • Rats, Sprague-Dawley
  • Selective Serotonin Reuptake Inhibitors / administration & dosage
  • Selective Serotonin Reuptake Inhibitors / pharmacokinetics*
  • Stereoisomerism*

Substances

  • Serotonin Uptake Inhibitors
  • Citalopram