Citalopram: interaction studies with levomepromazine, imipramine, and lithium.
The pharmacokinetic interactions between the selective serotonin reuptake inhibitor citalopram, given as an oral dose of 40 mg/day for 10 days, and (1) levomepromazine (50 mg single oral dose), (2) imipramine (100 mg single oral dose), and (3) lithium (30 mmol/day orally for 5 days) were examined in three panels each of 8 healthy young male volunteers (age 20-31). All volunteers were classified as extensive metabolizers of sparteine and mephenytoin. Each subject completed three study phases--one with citalopram alone, one with one of the three other drugs, alone, and one with citalopram combined with the corresponding other drug. For citalopram and its metabolites, a non-enantioselective analytical method (high-performance liquid chromatography) was used. Only two statistically significant interactions were indicated. First, levomepromazine caused a 10-20% increase from the initial steady-state levels of the primary citalopram metabolite, desmethylcitalopram. Second, citalopram caused approximately 50% increase in the single-dose area under the serum concentration/time curve of desipramine (primary metabolite or imipramine) and a corresponding reduction in the level of the subsequently formed metabolite 2-hydroxydesipramine. These findings are in agreement with the recent observations that (1) the demethylation of desmethylcitalopram (to didesmethylcytalopram) is partly mediated via the sparteine/debrisoquine oxygenase (CYP2D6) and that levomepromazine is a potent inhibitor of CYP2D6, and (2) that desmethylcitalopram has a somewhat stronger affinity for CYP2D6 than desipramine, and therefore may inhibit the hydroxylation of desipramine, which is also a substrate of CYP2D6.
Gram
L F
LF
Department of Clinical Pharmacology, Odense University, Denmark.
Hansen
M G
MG
Sindrup
S H
SH
Brøsen
K
K
Poulsen
J H
JH
Aaes-Jørgensen
T
T
Overø
K F
KF
D000328:Adult; D015283:Citalopram / Q000493:pharmacokinetics*; D004347:Drug Interactions; D006801:Humans; D007099:Imipramine / Q000493:pharmacokinetics*; D008094:Lithium / Q000493:pharmacokinetics*; D008297:Male; D008728:Methotrimeprazine / Q000493:pharmacokinetics*
D015283:Citalopram; D008094:Lithium; D008728:Methotrimeprazine; D007099:Imipramine