Tarumoto Y, Kimura M, Tokado H, Shinozawa R, Tsuchida T, Noda K, Nakane S, Sasajima M, Ohzeki M
J Toxicol Sci. 1981 Jul;6 Suppl:97-120. doi: 10.2131/jts.6.supplement_97.
Chronic toxicity of a new synthetic corticosteroid, hydrocortisone 17-butyrate 21-propionate (HBP), was investigated in rats of both sexes. HBP was percutaneously given to rats with 0.1%, 0.5% cream and ointment at the daily dose level of 150 mg per 100 g body weight for 6 months. For the comparison, the percutaneous toxicity with 0.12% betamethasone 17-valerate (BV) cream and ointment, and 0.1% hydrocortisone 17-butyrate (HB) cream and ointment at the daily dose level of 150 mg per 100 g body weight were studied. Rats receiving HBP showed the dose-dependent changes such as the suppression of body weight gain and food intake, emaciation, decrease in the number of white blood cells and lymphocytes, total protein, increase in the number of red cells, hematocrit, hemoglobin, blood sugar and total cholesterol, regressive changes in adrenal cortex, lymphatic and hematopoietic tissues and skin, and gastric erosion, which have been well known as toxic effects of synthetic corticosteroids. These findings were comparatively high toxic in male, and almost disappeared in rats elapsed recovery time of month after withdrawal of HBP. The toxicities of HBP, BV and HB were qualitatively same. However, the grade of effects of HBP toxicity was similar to that of HB, weaker than of BV.
研究了一种新型合成皮质类固醇17 - 丁酸氢化可的松21 - 丙酸酯(HBP)对雌雄大鼠的慢性毒性。以每日每100克体重150毫克的剂量水平,用0.1%、0.5%的乳膏和软膏经皮给予大鼠HBP,持续6个月。为作比较,还研究了以每日每100克体重150毫克的剂量水平,用0.12%的17 - 戊酸倍他米松(BV)乳膏和软膏以及0.1%的17 - 丁酸氢化可的松(HB)乳膏和软膏经皮给药的毒性。接受HBP的大鼠出现了剂量依赖性变化,如体重增加和食物摄入量受抑制、消瘦、白细胞和淋巴细胞数量减少、总蛋白减少、红细胞数量增加、血细胞比容增加、血红蛋白增加、血糖增加和总胆固醇增加,肾上腺皮质、淋巴和造血组织以及皮肤出现退行性变化,以及胃糜烂,这些都是合成皮质类固醇的众所周知的毒性作用。这些发现对雄性大鼠的毒性相对较高,且在停用HBP后经过一个月的恢复时间,大鼠的这些毒性几乎消失。HBP、BV和HB的毒性在性质上相同。然而,HBP毒性的作用程度与HB相似,比BV弱。