Steady-state pharmacokinetics of the enantiomers of citalopram and its metabolites in humans

✍ Scribed by Jagdev Sidhu; Morten Priskorn; Mette Poulsen; Alain Segonzac; Gilles Grollier; Frank Larsen

• Publisher: John Wiley and Sons
• Year: 1997
• Tongue: English
• Weight: 165 KB
• Volume: 9
• Category: Article
• ISSN: 0899-0042
• DOI: 10.1002/(sici)1520-636x(1997)9:7<686::aid-chir9>3.0.co;2-5

✦ Synopsis

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 t 1 /2 averaged 47 ± 11 and 35 ± 4 h and AUC ss averaged 4,193 ± 1,118 h ⅐ nmol/l and 2,562 ± 1,190 h ⅐ nmol/l. The observed enantiospecificities were apparently more related to clearance, rather than to distributional mechanisms.