Kawano S, Kondoh H, Ishikawa K, Koizumi S, Kadota T, Takahashi N
Preclinical Research Laboratories, Bristol-Myers Squibb K.K. Aichi, Japan.
J Toxicol Sci. 1994 Aug;19 Suppl 1:123-30. doi: 10.2131/jts.19.supplementi_123.
The vascular irritability of paclitaxel at concentrations of 0.6 and 1.2 mg/ml was examined using the rabbit ear vein by a single intravenous drip in comparison with its vehicle consisting of ethanol and Cremophor, and physiological saline. The results were as follows: 1. Slight to moderate congestion was macroscopically observed around some injection sites of the retroauricular veins infused by paclitaxel, the vehicle and saline. Its incidence and severity caused by paclitaxel was not so much different from that caused by the vehicle or saline. 2. Histopathological findings at the injection sites of the rabbits treated with paclitaxel consisted of vascular and perivascular changes, as well as alterations of the dermis and epidermis. These changes were severer than those brought by saline, and dose-dependent in their incidence and severity. Moreover, the lesions caused by paclitaxel at a concentration of 1.2 mg/ml were correspondent to those caused by the vehicle. Based on these results, the microscopic examinations suggested that the vascular irritability of paclitaxel might be attributable to administration of the vehicle.
采用兔耳静脉单次静脉滴注的方法，以含乙醇和聚氧乙烯蓖麻油的溶媒以及生理盐水作为对照，考察了浓度为0.6mg/ml和1.2mg/ml的紫杉醇的血管刺激性。结果如下：1. 在紫杉醇、溶媒和生理盐水注入的耳后静脉的一些注射部位周围，肉眼观察到轻微至中度充血。紫杉醇引起的充血发生率和严重程度与溶媒或生理盐水引起的没有太大差异。2. 用紫杉醇处理的兔子注射部位的组织病理学结果包括血管和血管周围变化，以及真皮和表皮的改变。这些变化比生理盐水引起的更严重，并且在发生率和严重程度上呈剂量依赖性。此外，浓度为1.2mg/ml的紫杉醇引起的病变与溶媒引起的病变相对应。基于这些结果，显微镜检查表明紫杉醇的血管刺激性可能归因于溶媒的给药。
