Postmortem redistribution of the enantiomers of citalopram and its metabolites: an experimental study in rats.
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.
Kugelberg
Fredrik C
FC
Division of Clinical Pharmacology, Department of Medicine and Care, Faculty of Health Sciences, Linköping University, SE-581 85 Linköping, Sweden. fredrik.kugelberg@imv.liu.se
Druid
Henrik
H
Carlsson
Björn
B
Ahlner
Johan
J
Bengtsson
Finn
F
D000818:Animals; D015283:Citalopram / Q000008:administration & dosage / Q000493:pharmacokinetics*; D004305:Dose-Response Relationship, Drug; D015918:Infusion Pumps, Implantable; D007279:Injections, Subcutaneous; D008297:Male; D009995:Osmosis; D011180:Postmortem Changes; D051381:Rats; D017207:Rats, Sprague-Dawley; D017367:Selective Serotonin Reuptake Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics*; D013237:Stereoisomerism
D015283:Citalopram; D017367:Selective Serotonin Reuptake Inhibitors