Single-dose pharmacokinetics and pharmacodynamics of oral triazolam in relation to cytochrome P4502C19 (CYP2C19) activity.

Previous studies have suggested that triazolam is at least partly metabolized by cytochrome P4503A4 (CYP3A4). However, no study has examined the relationship between the metabolism of triazolam and CYP2C19, which is involved in the metabolism of diazepam. Therefore, the single-dose pharmacokinetics and pharmacodynamics of oral triazolam were studied in relation to the CYP2C19 status assessed by the S-mephenytoin 4-hydroxylation capacity in 12 healthy male volunteers, consisting of seven extensive metabolizers (EMs) and five poor metabolizers (PMs) of S-mephenytoin 4-hydroxylation. Each subject was administered a single oral dose of 0.5 mg of triazolam, and blood was sampled up to 12 hours after the dosing. Psychomotor function was assessed by the Digit-Symbol Substitution test, Visual Analogue Scale, and Udvalg for Kliniske Undersøgelser (UKU) scale. Plasma triazolam concentrations were measured by high-performance liquid chromatography. There were no significant differences in plasma concentrations from 20 minutes to 6 hours after the dosing nor in pharmacokinetic parameters of triazolam between the EM and PM groups. No significant difference was found in psychomotor function between the EM and PM groups. These results suggest that CYP2C19 is not involved in the metabolism of triazolam and that CYP2C19 status is not a pharmacodynamic determinant of this triazolobenzodiazepine.