Høgskilde S, Nielsen J W, Carl P, Angelo H, Bredgaard Sørensen M
Acta Anaesthesiol Scand. 1987 May;31(4):289-91. doi: 10.1111/j.1399-6576.1987.tb02568.x.
The anticonvulsive activity (ED50), acute toxicity (LD50), and minimal neurotoxicity (TD50) of diazepam in an emulsion form (Diazemuls) were compared with two different water-based diazepam solutions (Valium and Stesolid). The diazepam preparations were administered intravenously to male mice. After determination of time of peak drug activity, the ED50's were established against pentetrazol-induced convulsions, at peak drug activity. The most important difference between the three diazepam preparations was a significantly higher LD50 of diazemuls (275 mg/kg) compared to valium (49 mg/kg) and stesolid (51 mg/kg). ED50 was: diazemuls 0.24 mg/kg, valium 0.14 mg/kg and stesolid 0.10 mg/kg. The therapeutic indices (LD50/ED50) were thus calculated to be 1146 for diazemuls, 350 for valium and 510 for stesolid. Time of peak drug activity and TD50 were equal for all three drugs. No signs of pain on injection or necrosis were observed following diazemuls, whereas this was common after valium and stesolid.
将乳剂形式的地西泮（安定乳剂）的抗惊厥活性（半数有效量，ED50）、急性毒性（半数致死量，LD50）和最小神经毒性（最小中毒量，TD50）与两种不同的水基地西泮溶液（安定和去甲羟基安定）进行了比较。将地西泮制剂静脉注射给雄性小鼠。在确定药物活性峰值时间后，在药物活性峰值时测定针对戊四氮诱导惊厥的ED50。三种地西泮制剂之间最重要的差异是，与安定（49毫克/千克）和去甲羟基安定（51毫克/千克）相比，安定乳剂的LD50显著更高（275毫克/千克）。ED50分别为：安定乳剂0.24毫克/千克、安定0.14毫克/千克和去甲羟基安定0.10毫克/千克。因此，计算出的治疗指数（LD50/ED50）分别为：安定乳剂1146、安定350和去甲羟基安定510。三种药物的药物活性峰值时间和TD50相同。注射安定乳剂后未观察到注射疼痛或坏死迹象，而在注射安定和去甲羟基安定后这很常见。
