Lack of interaction between citalopram and the CYP3A4 substrate triazolam

Study Objectives. 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. Design. Open-label, multidose study. Setting. Clinical Studies, Ltd., Fort Lauderdale, Florida. Participants. Eighteen healthy male and female volunteers. Interventions. 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. Measurements and Main 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. Conclusion. No pharmacokinetic interaction between the drugs was observed, suggesting that triazolam and other cytochrome P450 3A4 substrates can be coadministered safely with citalopram.