To investigate pharmacokinetic and pharmacodynamic differences of zolpidem between males and females and their causes, including CYP3A4 activity. A single oral dose of zolpidem (10 mg) was administered to 15 male and 15 female healthy subjects. Blood samples were collected up to 12 h post-dose to determine plasma zolpidem concentrations. Pharmacokinetic parameters were obtained using non-compartmental analysis. Digit symbol substitution test, choice reaction time, and visual analog scale of sleepiness were used to evaluate pharmacodynamics. We measured CYP3A4 activity using 4β-hydroxycholesterol, an endogenous metabolite. Mean maximum plasma concentration and area under the plasma concentration–time curve were higher for females than for males (9.9% and 32.5%, respectively); other pharmacokinetic parameters showed no significant differences. Pharmacodynamic scores for females showed delayed recovery compared with that for males. CYP3A4 activity was higher in females than in males (p = 0.030). There was no serious adverse event, and adverse event incidence was not different between the sexes. Zolpidem exposure was about 30% higher in females than in males. Delayed pharmacodynamic score recovery in females could be related to higher zolpidem concentrations. Although apparent clearance was lower in females, systemic clearance might not be the cause of the different exposures to zolpidem.

研究唑吡坦在男性和女性之间的药代动力学和药效学差异及其原因，包括 CYP3A4 活性。给 15 名男性和 15 名女性健康受试者单次口服剂量的唑吡坦（10 毫克）。在给药后 12 小时内收集血样以确定血浆唑吡坦浓度。使用非房室分析获得药代动力学参数。使用数字符号替换测试、选择反应时间和嗜睡的视觉模拟量表来评估药效学。我们使用内源性代谢物 4β-羟基胆固醇测量了 CYP3A4 活性。女性的平均最大血浆浓度和血浆浓度-时间曲线下面积高于男性（分别为 9.9% 和 32.5%）；其他药代动力学参数无显着差异。与男性相比，女性的药效学评分显示恢复延迟。CYP3A4 活性在女性中高于男性（p  = 0.030）。无严重不良事件，不良事件发生率无性别差异。女性的唑吡坦暴露量比男性高约 30%。女性药效学评分恢复延迟可能与较高的唑吡坦浓度有关。尽管女性的表观清除率较低，但全身清除率可能不是唑吡坦不同暴露的原因。