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Pharmacology. 1999 Dec;59(6):298-309.

Studies on the stereoselective metabolism of citalopram by human liver microsomes and cDNA-expressed cytochrome P450 enzymes.

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  • 1Institute for Basic Psychiatric Research, Department of Biological Psychiatry, Psychiatric Hospital in Aarhus, Aarhus University Hospital, Risskov, Denmark. viol1907@post3.tele.dk

Abstract

The involvement of CYP enzymes in the metabolism of citalopram was studied, inclusive the conversion of demethylcitalopram to didemethylcitalopram and the formation of citalopram N-oxide, which both have not been considered previously. Using human mixed liver microsomes and cDNA-expressed CYP enzymes, we confirmed that CYP3A4, 2C19 and 2D6 are involved in the first demethylation step of citalopram, all favouring conversion of the biologically active S-enantiomer. Inhibitor studies indicated that at therapeutic citalopram concentrations CYP3A4 was responsible for 40-50% of demethylcitalopram formation, while the contribution of CYP2C19 increased and that of CYP2D6 tended to decrease with increasing drug concentration. CYP2D6 exclusively mediated the second demethylation step, and citalopram N-oxide was also exclusively formed by CYP2D6. None of the studied CYP enzymes mediated deamination to the propionic acid derivative.

Copyright 1999 S. Karger AG, Basel

PMID:
10575324
[PubMed - indexed for MEDLINE]
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