Al-Tahan F, Löscher W, Frey H H
Arch Int Pharmacodyn Ther. 1984 Apr;268(2):180-93.
After i.v. administration of 0.2 mg/kg clonazepam to dogs, plasma concentrations followed partly a biexponential and partly a monoexponential decline, the terminal elimination half-life (t0.5 beta or t0.5) being 1.4 +/- 0.3 hr. Over the dose range from 0.1 to 0.5 mg/kg the elimination rate was dose-dependent. At the highest dose level, one dog showed signs of a saturation kinetics. After oral administration absorption was rapid, but bioavailability poor and highly variable (20-60%). In spite of the high elimination rate in the single dose studies, clonazepam plasma concentrations in the range known as "therapeutic" in man could be maintained in subacute studies (1 week) by dosing 0.5 mg/kg b.i.d. or t.i.d. This is most likely explained by a saturation of metabolic inactivation and makes the dog a useful model for man when the drug is given continuously. Protein binding averaged 82% and is thus similar to man. Clonazepam passed the blood/CSF barrier rapidly (P = 0.217 min-1) so that steady state conditions were reached within 10-20 min.
给犬静脉注射0.2mg/kg氯硝西泮后，血浆浓度部分呈双指数下降，部分呈单指数下降，终末消除半衰期（t0.5β或t0.5）为1.4±0.3小时。在0.1至0.5mg/kg的剂量范围内，消除速率呈剂量依赖性。在最高剂量水平时，一只犬表现出饱和动力学的迹象。口服给药后吸收迅速，但生物利用度低且高度可变（20%-60%）。尽管在单剂量研究中消除速率较高，但在亚急性研究（1周）中，通过每天给药0.5mg/kg，分两次或三次给药，可维持人“治疗”范围内的氯硝西泮血浆浓度。这很可能是由于代谢失活饱和所致，当持续给药时，犬成为人的有用模型。蛋白结合率平均为82%，因此与人类相似。氯硝西泮迅速通过血脑屏障（P=0.217分钟-1），因此在10-20分钟内达到稳态。
