Steady-state pharmacokinetics of the enantiomers of citalopram and its metabolites in humans.
The steady-state pharmacokinetics in serum and urine of the enantiomers of citalopram and its metabolites, demethylcitalopram (DCT) and didemethylcitalopram (DDCT), were investigated after multiple doses of rac-citalopram for 21 consecutive days (40 mg per day) to healthy human subjects who were extensive metabolisers of sparteine and mephenytoin. Comparable pharmacokinetic variability was noted for (+)-(S)-, (-)-(R)- and rac-citalopram. Enantiomeric (S/R) serum concentration ratios for citalopram were always less than unity and were constant during the steady-state dosing interval. A modest, but statistically significant, stereoselectivity in the disposition of citalopram and its two main metabolites was observed. Serum levels of the (+)-(S)-enantiomers of citalopram, DCT, and DDCT throughout the steady-state dosing interval investigated were 37 +/- 6%, 42 +/- 3% and 32 +/- 3%, respectively, of their total racemic serum concentrations. The (+)-(S)-enantiomers of citalopram, DCT, and DDCT were eliminated faster than their antipodes. For (-)-(R)- and (+)-(S)-citalopram, respectively, the serum t1/2 averaged 47 +/- 11 and 35 +/- 4 h and AUCss averaged 4,193 +/- 1,118 h.nmol/l and 2,562 +/- 1,190 h.nmol/l. The observed enantiospecificities were apparently more related to clearance, rather than to distributional mechanisms.
Sidhu
J
J
Department of Pharmacokinetics/Dynamics, H. Lundbeck A/S, Copenhagen, Denmark.
Priskorn
M
M
Poulsen
M
M
Segonzac
A
A
Grollier
G
G
Larsen
F
F
D000328:Adult; D000928:Antidepressive Agents / Q000737:chemistry* / Q000378:metabolism / Q000493:pharmacokinetics*; D001711:Biotransformation; D002851:Chromatography, High Pressure Liquid; D015283:Citalopram / Q000031:analogs & derivatives / Q000737:chemistry* / Q000378:metabolism / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D008297:Male; D013237:Stereoisomerism
D000928:Antidepressive Agents; D015283:Citalopram; C054417:monodesmethylcitalopram; C064735:didesmethylcitalopram