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Steady-state pharmacokinetics of the enantiomers of citalopram and its metabolites in humans
- Source :
- Chirality. 9:686-692
- Publication Year :
- 1997
- Publisher :
- Wiley, 1997.
-
Abstract
- 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.
- Subjects :
- Adult
Male
Urine
Citalopram
Pharmacology
behavioral disciplines and activities
Catalysis
Analytical Chemistry
Pharmacokinetics
mental disorders
Drug Discovery
medicine
Humans
Mephenytoin
Biotransformation
Chromatography, High Pressure Liquid
Spectroscopy
Chemistry
Organic Chemistry
Sparteine
Stereoisomerism
Antidepressive Agents
Female
Stereoselectivity
Steady state (chemistry)
Enantiomer
medicine.drug
Subjects
Details
- ISSN :
- 1520636X and 08990042
- Volume :
- 9
- Database :
- OpenAIRE
- Journal :
- Chirality
- Accession number :
- edsair.doi.dedup.....62549fde7eec78e4d6a288b65cd0e766