血浆地西泮浓度的昼夜变化与游离分数的相应变化相关。
Diurnal variations in plasma diazepam concentrations associated with reciprocal changes in free fraction.
作者信息
Naranjo C A, Sellers E M, Giles H G, Abel J G
出版信息
Br J Clin Pharmacol. 1980 Mar;9(3):265-72. doi: 10.1111/j.1365-2125.1980.tb04836.x.
1 The characteristics and mechanism of fluctuations in diazepam and N-desmethyldiazepam concentrations and diazepam free fraction were studied in six volunteers, who received diazepam (10 mg, i.v. over 20 min) and in five chronic diazepam users. 2 Within a day total diazepam and N-desmethyldiazepam concentrations varied significantly (P less than 0.001) and were lower than predicted between 23.00 and 08.00 h and higher by 09.00 h. In contrast, diazepam free fraction also varied significantly (P less than 0.001) and was highest between 23.00 and 08.00 h and lower by 09.00 h. Coincident increases in total diazepam concentrations (P less than 0.005) and decreases in diazepam free fraction were associated with food intake (P less than 0.05). 3 The coincident diurnal variations in diazepam and N-desmethyldiazepam concentrations and the negative correlation between total diazepam concentration and diazepam free fraction (r = 0.73, P less than 0.001) suggest that the mechanism of the fluctuations is intravascular and tissue redistribution rather than effect on drug biotransformation. 4 These variations may introduce large between and within investigator experimental differences in the determination of kinetic parameters. Free drug concentration varies over the day, and within day variations in clinical effect may be observed.
- 研究了6名志愿者静脉注射地西泮（10 mg，20分钟内注射完毕）后以及5名长期使用地西泮者体内地西泮和N-去甲基地西泮浓度及地西泮游离分数的波动特征和机制。2. 在一天之内，地西泮和N-去甲基地西泮的总浓度变化显著（P<0.001），在23:00至08:00之间低于预测值，到09:00时升高。相比之下，地西泮游离分数也变化显著（P<0.001），在23:00至08:00之间最高，到09:00时降低。地西泮总浓度的同时升高（P<0.005）和地西泮游离分数的降低与食物摄入有关（P<0.05）。3. 地西泮和N-去甲基地西泮浓度的同步昼夜变化以及地西泮总浓度与地西泮游离分数之间的负相关（r = 0.73，P<0.001）表明，波动机制是血管内和组织再分布，而非对药物生物转化的影响。4. 这些变化可能在动力学参数测定中导致研究者之间以及研究者内部出现较大的实验差异。游离药物浓度在一天中有所变化，并且可能观察到临床效应在一天内的变化。
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