Stereoselective single-dose kinetics of citalopram and its metabolites in rats

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.