Greenblatt D J, Allen M D, Harmatz J S, Shader R I
Clin Pharmacol Ther. 1980 Mar;27(3):301-12. doi: 10.1038/clpt.1980.40.
Factors influencing diazepam kinetics were assessed in 4 equal groups (n = 11) of young male and female (aged 21 to 37 yr) and elderly male and female (aged 61 to 84 yr) subjects, all of whom were healthy. In all 44, plasma diazepam concentrations were determined by electron-capture gas-liquid chromatography in multiple samples drawn for as long as 9 days after a single 5- to 10-mg intravenous dose. Based upon total (bound + free) diazepam concentrations, volume of distribution (Vd) ranged from 0.7 to 4.7 l/kg, and became larger both with increasing age and with female sex. Clearances of total (bound + free) diazepam in young and elderly females were nearly identical (0.51 and 0.48 ml/min/kg), but clearance was higher in young than elderly males (0.39 and 0.24 ml/min/kg, p less than 0.01). The unbound fraction of diazepam in plasma (range, 0.9% to 2.7%) did not depend on sex, but was greater in the elderly than in the young. In part this related to lower plasma albumin concentrations in the elderly. After correction of kinetic data for individual differences in free fraction, Vd was larger in the females than in the males, but the effect of age was small. Clearance of unbound diazepam (intrinsic clearance) tended to be higher in the females than in the males of both age groups, and was higher in the young than in the elderly of both sexes (male: 29.9 and 14.9 ml/min/kg, p less than 0.005; female: 43.6 and 28.0 ml/min/kg, p less than 0.05). Smoking was associated with higher clearance values, particularly among young subjects.
在4组每组11名的年轻男性和女性（年龄21至37岁）以及老年男性和女性（年龄61至84岁）健康受试者中评估了影响地西泮动力学的因素。在44名受试者中，单次静脉注射5至10毫克后，长达9天内多次采集样本，通过电子捕获气液色谱法测定血浆地西泮浓度。基于总（结合 + 游离）地西泮浓度，分布容积（Vd）范围为0.7至4.7升/千克，并且随着年龄增长和女性性别而增大。年轻和老年女性中总（结合 + 游离）地西泮的清除率几乎相同（分别为0.51和0.48毫升/分钟/千克），但年轻男性的清除率高于老年男性（分别为0.39和0.24毫升/分钟/千克，p < 0.01）。血浆中地西泮的游离分数（范围为0.9%至2.7%）不取决于性别，但老年人高于年轻人。部分原因与老年人血浆白蛋白浓度较低有关。在对游离分数的个体差异进行动力学数据校正后，女性的Vd大于男性，但年龄的影响较小。两个年龄组中，女性游离地西泮的清除率（内在清除率）均倾向于高于男性，并且两性中年轻人的清除率均高于老年人（男性：29.9和14.9毫升/分钟/千克，p < 0.005；女性：43.6和28.0毫升/分钟/千克，p < 0.05）。吸烟与较高的清除率值相关，尤其是在年轻受试者中。
