Yasui N, Otani K, Ohkubo T, Osanai T, Sugawara K, Chiba K, Ishizaki T, Kaneko S
Department of Neuropsychiatry, Hirosaki University Hospital, Japan.
Ther Drug Monit. 1997 Aug;19(4):371-4. doi: 10.1097/00007691-199708000-00001.
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.
以往的研究表明，三唑仑至少部分是由细胞色素P4503A4（CYP3A4）代谢的。然而，尚无研究考察三唑仑代谢与参与地西泮代谢的CYP2C19之间的关系。因此，在12名健康男性志愿者中，根据S-美芬妥因4-羟化能力评估的CYP2C19状态，研究了口服三唑仑的单剂量药代动力学和药效学，其中包括7名S-美芬妥因4-羟化的快代谢者（EMs）和5名慢代谢者（PMs）。每位受试者口服单剂量0.5mg三唑仑，并在给药后长达12小时采集血样。通过数字符号替换试验、视觉模拟量表和临床检查丹麦语量表（UKU）评估精神运动功能。血浆三唑仑浓度通过高效液相色谱法测定。给药后20分钟至6小时，EM组和PM组的血浆浓度以及三唑仑的药代动力学参数均无显著差异。EM组和PM组在精神运动功能方面未发现显著差异。这些结果表明，CYP2C19不参与三唑仑的代谢，且CYP2C19状态不是这种三唑并苯二氮䓬类药物的药效学决定因素。
