Enantioselective analysis of citalopram and metabolites in adolescents.
Studies of the antidepressant effect and pharmacokinetics of citalopram have been performed in adults, but the effects on children and adolescents have only been studied to a minor extent despite its increasing use in these age groups. The aim of this study was to investigate a group of adolescents treated for depression, with respect to the steady-state plasma concentrations of the enantiomers of citalopram and its demethylated metabolites desmethylcitalopram and didesmethylcitalopram. Moreover, the authors studied the genotypes for the polymorphic cytochrome P450 enzymes CYP2D6 and CYP2C19 in relation to the different enantiomers. The S/R ratios of citalopram and desmethylcitalopram found in this study of 19 adolescents were similar to studies involving older patients. The concentrations of the R-(-)- and S-(+)-enantiomers of citalopram and desmethylcitalopram were also in agreement with values from earlier studies, the R-(-)-enantiomer (distomer) being the major enantiomer. The results indicate that the use of oral contraceptives may have some influence on the metabolism of citalopram. This might be because of an interaction of the contraceptive hormones with the CYP2C19 enzyme.
Carlsson
B
B
Division of Clinical Pharmacology, Department of Medicine and Care, Faculty of Health Sciences, Linköping University, Sweden. bjorn.carlsson.lio.se
Olsson
G
G
Reis
M
M
Walinder
J
J
Nordin
C
C
Lundmark
J
J
Scordo
M G
MG
Dahl
M L
ML
Bengtsson
F
F
Ahlner
J
J
D000293:Adolescent; D000928:Antidepressive Agents / Q000097:blood*; D001189:Aryl Hydrocarbon Hydroxylases; D015283:Citalopram / Q000097:blood* / Q000737:chemistry / Q000378:metabolism; D065731:Cytochrome P-450 CYP2C19; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics; D005838:Genotype; D006801:Humans; D006899:Mixed Function Oxygenases / Q000235:genetics; D013237:Stereoisomerism
D000928:Antidepressive Agents; D015283:Citalopram; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D019389:Cytochrome P-450 CYP2D6