Muir W W, Sams R A, Huffman R H, Noonan J S
Am J Vet Res. 1982 Oct;43(10):1756-62.
The cardiopulmonary, behavioral, and pharmacokinetic properties of diazepam were determined in horses. Heart rate, cardiac output, mean pulmonary artery, aortic and right atrial blood pressures, respiratory rate, and arterial pH and blood gas values did not change after IV diazepam (0.05, 0.1, 0.2, 0.4 mg/kg) administration. Increasing doses of diazepam resulted in signs of muscle weakness including fixed stance, muscle fasciculations of the head, neck, and thorax muscles, ataxia, and then recumbency. Dosages of diazepam exceeding 0.2 mg/kg produced mild sedation. Behavioral changes persisted for up to 2 hours with a dosage of 0.4 mg/kg. Plasma concentration-time data in horses given brief (5 min) infusions of diazepam were described by a triexponential equation. Total body clearances of diazepam were between 6.94 and 9.56 ml/min/kg, and the half-life values between 2.52 and 21.6 hours. The volume of distribution at steady state was 1.56 to 2.94 L/kg. N-Desmethyldiazepam was identified by gas chromatography-mass spectrometry following glucuronide hydrolysis of urine. Oxazepam, N-methyloxazepam, and N-desmethyldiazepam, but not diazepam, were detected after glucuronide hydrolysis of urine collected from 1 horse which was given 140 mg of IV diazepam. Only N-desmethyldiazepam was detected in hydrolyzed urine samples collected from other horses given 80 mg of diazepam.
在马匹中测定了地西泮的心肺、行为和药代动力学特性。静脉注射地西泮（0.05、0.1、0.2、0.4mg/kg）后，心率、心输出量、平均肺动脉压、主动脉压和右心房血压、呼吸频率以及动脉pH值和血气值均未改变。地西泮剂量增加会导致肌肉无力的体征，包括姿势固定、头部、颈部和胸部肌肉的肌束震颤、共济失调，随后出现卧倒。超过0.2mg/kg的地西泮剂量会产生轻度镇静作用。剂量为0.4mg/kg时，行为改变可持续长达2小时。给予马匹短暂（5分钟）输注地西泮后的血浆浓度-时间数据可用三指数方程描述。地西泮的全身清除率在6.94至9.56ml/（min·kg）之间，半衰期值在2.52至21.6小时之间。稳态分布容积为1.56至2.94L/kg。尿液经葡萄糖醛酸苷水解后，通过气相色谱-质谱法鉴定出N-去甲基地西泮。在1匹静脉注射140mg地西泮的马收集的尿液经葡萄糖醛酸苷水解后，检测到奥沙西泮、N-甲基奥沙西泮和N-去甲基地西泮，但未检测到地西泮。在其他给予80mg地西泮的马收集的水解尿液样本中仅检测到N-去甲基地西泮。
