Lack of interaction between citalopram and the CYP3A4 substrate triazolam.
OBJECTIVE
To determine the effect of the selective serotonin reuptake inhibitor citalopram on plasma levels of triazolam, and to determine the effect of a single dose of triazolam on steady-state levels of citalopram and its major metabolites.


METHODS
Open-label, multidose study.


METHODS
Clinical Studies, Ltd., Fort Lauderdale, Florida.


METHODS
Eighteen healthy male and female volunteers.


METHODS
Subjects received triazolam 0.25 mg alone and another 0.25-mg dose after 4 weeks of citalopram 20 mg/day for 1 week, followed by 3 weeks of citalopram 40 mg/day


RESULTS
Pharmacokinetic parameters were determined after single-dose administration of triazolam alone, after administration of citalopram alone at steady state, and after coadministration of the drugs. The pharmacokinetics of triazolam and its metabolite alpha-hydroxytriazolam were unchanged by citalopram coadministration. Triazolam appeared to be absorbed slightly more quickly during coadministration. Citalopram kinetics were unaffected by coadministration.


CONCLUSIONS
No pharmacokinetic interaction between the drugs was observed, suggesting that triazolam and other cytochrome P450 3A4 substrates can be coadministered safely with citalopram.
Nolting
A
A
Department of Pharmacokinetics, Forest Laboratories, Inc., New York, New York 10022, USA.
Abramowitz
W
W
D000328:Adult; D000928:Antidepressive Agents / Q000009:adverse effects*; D019540:Area Under Curve; D015283:Citalopram / Q000009:adverse effects*; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004347:Drug Interactions; D005260:Female; D006801:Humans; D006993:Hypnotics and Sedatives / Q000097:blood / Q000493:pharmacokinetics*; D008297:Male; D006899:Mixed Function Oxygenases / Q000378:metabolism*; D014229:Triazolam / Q000097:blood / Q000493:pharmacokinetics*
D000928:Antidepressive Agents; D006993:Hypnotics and Sedatives; D015283:Citalopram; D014229:Triazolam; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; C104464:CYP3A protein, human; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human