Enantioselective analysis of citalopram and its metabolites in postmortem blood and genotyping for CYD2D6 and CYP2C19.
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.
Holmgren
Per
P
National Board of Forensic Medicine, Department of Forensic Chemistry, Faculty of Health Science, Linköping University, S-581 85 Linköping, Sweden. per.holmgren@rmv.se
Carlsson
Björn
B
Zackrisson
Anna-Lena
AL
Lindblom
Bertil
B
Dahl
Marja-Liisa
ML
Scordo
Maria Gabriella
MG
Druid
Henrik
H
Ahlner
Johan
J
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001189:Aryl Hydrocarbon Hydroxylases / Q000097:blood / Q000235:genetics*; D002423:Cause of Death; D002851:Chromatography, High Pressure Liquid; D015283:Citalopram / Q000031:analogs & derivatives / Q000097:blood* / Q000493:pharmacokinetics; D065731:Cytochrome P-450 CYP2C19; D019389:Cytochrome P-450 CYP2D6 / Q000097:blood / Q000235:genetics*; D004247:DNA / Q000032:analysis; D005260:Female; D005554:Forensic Medicine / Q000379:methods; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D006899:Mixed Function Oxygenases / Q000097:blood / Q000235:genetics*; D017367:Selective Serotonin Reuptake Inhibitors / Q000097:blood* / Q000493:pharmacokinetics; D013237:Stereoisomerism; D015813:Substance Abuse Detection / Q000379:methods*; D013997:Time Factors
D001189:Aryl Hydrocarbon Hydroxylases; D015283:Citalopram; D065731:Cytochrome P-450 CYP2C19; D019389:Cytochrome P-450 CYP2D6; D004247:DNA; D006899:Mixed Function Oxygenases; D017367:Selective Serotonin Reuptake Inhibitors; C045793:CYP2C19 protein, human