Johnson R F, Schenker S, Roberts R K, Desmond P V, Wilkinson G R
J Pharm Sci. 1979 Oct;68(10):1320-2. doi: 10.1002/jps.2600681034.
Plasma binding of chlordiazepoxide, diazepam, loraxepam, and oxazepam was determined by equilibrium dialysis in 20 male, healthy volunteers, 25-86 years old. A wide range of binding was observed, with the free fraction varying twofold for lorazepam, fourfold for chlordiazepoxide and diazepam, and over 20-fold for oxazepam. Statistically significant linear relationships were not observed between the degree of binding and age, serum albumin, or total protein for any of the drugs. There was, however, a correlation between the extent of binding for the four drugs. Because of the importance of unbound benzodiazepine levels in eliciting any pharmacological response and also in disposition, consideration of the wide interindividual variability in plasma binding must be made in interpreting pharmacodynamic and pharmacokinetic data.
通过平衡透析法测定了20名年龄在25至86岁之间的健康男性志愿者血浆中氯氮卓、地西泮、劳拉西泮和奥沙西泮的结合情况。观察到结合范围较广，劳拉西泮的游离分数变化两倍，氯氮卓和地西泮变化四倍，奥沙西泮变化超过20倍。对于任何一种药物，结合程度与年龄、血清白蛋白或总蛋白之间均未观察到具有统计学意义的线性关系。然而，这四种药物的结合程度之间存在相关性。由于未结合苯二氮䓬水平在引发任何药理反应以及药物处置方面都很重要，因此在解释药效学和药代动力学数据时，必须考虑血浆结合中个体间的广泛变异性。
