Stereoselective single-dose kinetics of citalopram and its metabolites in rats
2003 (English)In: Chirality, ISSN 0899-0042, E-ISSN 1520-636X, Vol. 15, no 7, 622-629 p.Article in journal (Refereed) Published
The single-dose kinetics of the enantiomers of citalopram (CIT) and its metabolites, demethylcitalopram (DCIT) and didemethylcitalopram (DDCIT), were investigated after administration of 10, 20, or 100 mg/kg (s.c.) rac-CIT to rats. Samples from serum and two brain regions were collected 1, 3, 10, or 20 h postdose for HPLC analysis. In the 100 mg/kg rats, the enantiomeric (S/R) serum concentration ratios of CIT decreased during the study period (0.93 at 1 h vs. 0.59 at 20 h; P < 0.001). In the 10 and 20 mg/kg rats, the decrease in serum S/R CIT ratios was not so evident as in the 100 mg/kg rats. In all three groups the S/R CIT ratio was almost the same in the brain as in serum, although both CIT enantiomer levels in the brain were found to be 5–10 times higher than the levels in serum. The serum and brain metabolite levels were low in the 10 and 20 mg/kg rats, whereas the levels increased during the study period in the 100 mg/kg rats. In conclusion, the CIT enantiomers were shown for the first time to be stereoselectively metabolized after single-dose administration to rats, as previously shown in steady-state dosing studies in humans and rats. Chirality 15:622–629, 2003. © 2003 Wiley-Liss, Inc.
Place, publisher, year, edition, pages
2003. Vol. 15, no 7, 622-629 p.
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:liu:diva-26746DOI: 10.1002/chir.10266Local ID: 11341OAI: oai:DiVA.org:liu-26746DiVA: diva2:247296