Jostell K G, Agurell S, Allgén L G, Kuylenstierna B, Lindgren J E, Aberg G, Osterlöf G
Acta Pharmacol Toxicol (Copenh). 1978 Sep;43(3):180-9. doi: 10.1111/j.1600-0773.1978.tb02253.x.
The systemic availability of clomethiazole was assessed by comparing blood levels after intravenous and oral administration. Clomethiazole was rapidly absorbed after oral administration to volunteers, particularly when administered as syrup. The fraction of the given dose that reached the systemic circulation after 1 capsule of clomethiazole (192 mg clomethiazole) was 0.25 +/- 0.18, after 2 capsules (384 mg clomethiazole) 0.38 +/- 0.18, and after 15 ml syrup (480 mg clomethiazole) 0.42 +/- 0.20. The time-blood concentration profiles were consistent with a two-compartment open model and the mean elimination half-lives of 3.6--5.0 hrs. were found for the different formulations and administration routes. Elimination half-lives showed little variation and a mean systemic clearance of 49 ml/min./kg was found for clomethiazole after intravenous administration. Clomethiazole is bound to human plasma proteins (63.4 +/- 1.6%, 37 degrees), a binding which is not affected by Vacutainer sample tubes. The blood/plasma distribution of clomethiazole was 0.76 +/- 0.02 at 37 degrees. A sensitive mass fragmentographic assay for the determination of clomethiazole in blood/plasma down to levels of 1 ng/ml (6.2 nmol/l) is described.
通过比较静脉注射和口服后血药浓度来评估氯美噻唑的全身可用性。氯美噻唑口服后能迅速被志愿者吸收，尤其是制成糖浆剂服用时。服用1粒氯美噻唑胶囊（192mg氯美噻唑）后，进入体循环的给药剂量分数为0.25±0.18；服用2粒胶囊（384mg氯美噻唑）后为0.38±0.18；服用15ml糖浆剂（480mg氯美噻唑）后为0.42±0.20。血药浓度-时间曲线符合二室开放模型，不同剂型和给药途径的平均消除半衰期为3.6 - 5.0小时。消除半衰期变化不大，静脉注射后氯美噻唑的平均全身清除率为49ml/min./kg。氯美噻唑与人体血浆蛋白结合（37℃时为63.4±1.6%），这种结合不受真空采血管的影响。37℃时氯美噻唑的血/血浆分布系数为0.76±0.02。本文描述了一种灵敏的质量碎片分析法，用于测定血/血浆中低至1ng/ml（6.2nmol/l）的氯美噻唑。
