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

Article Details

Citation

Olesen OV, Linnet K

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

Pharmacology. 1999 Dec;59(6):298-309. doi: 10.1159/000028333.

PubMed ID
10575324 [ View in PubMed
]
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.

DrugBank Data that Cites this Article

Drug Enzymes
DrugEnzymeKindOrganismPharmacological ActionActions
CitalopramCytochrome P450 2C19ProteinHumans
No
Substrate
Inhibitor
Details
Drug Reactions
Reaction
Details