Nagashima Y, Ide M, Akai H, Tamura K, Shimura K, Tanaka H, Tanaka G
Bozo Research Center Inc., Tokyo, Japan.
J Toxicol Sci. 1992 Nov;17 Suppl 3:161-99. doi: 10.2131/jts.17.supplementiii_161.
The toxicity of Prednisolone farnesylate (PNF) gel, a synthetic glucocorticoid, was investigated in the Beagle dog. PNF gel was administered percutaneously at doses of 0.05, 0.2 and 0.8 mg/kg/day for 52 weeks, then the drug was with held for 8 weeks to evaluate reversibility. The results are summarized in the following. 1. In the 0.05 mg/kg/day and above groups, hypotrichosis in the application site of the skin, thinning of the skin and atrophy of the appendages, and in the 0.2 mg/kg/day and above groups a tendency toward retarded body weight gain, were observed. 2. In the 0.2 mg/kg/day and above groups, a drop in the lymphocyte ratio, a rise in GOT activity and A1P level, and in the 0.8 mg/kg/day group a rise in free fatty acid were observed. 3. In the 0.2 mg/kg/day group and above groups, atrophy of the zona fasciculata and zona reticularis were observed. In the 0.8 mg/kg/day group, a decrease in the weight of the thymus and adrenal glands, and a increase in the weight of the liver, were observed. 4. At the end of the recovery period, most of the changes disappeared, except for those in the adrenals and treated area. From the above results, under the conditions of this study, it was concluded that when the changes observed in the application site of the skin in each group were not taken into consideration, the toxicological no effect level was 0.05 mg/kg/day for both males and females and the overt toxic dose level was 0.8 mg/kg/day.
对一种合成糖皮质激素法尼醇泼尼松龙（PNF）凝胶在比格犬身上进行了毒性研究。以0.05、0.2和0.8mg/kg/天的剂量经皮给予PNF凝胶，持续52周，然后停药8周以评估可逆性。结果总结如下：1. 在0.05mg/kg/天及以上剂量组，观察到皮肤涂抹部位脱毛、皮肤变薄和附属器萎缩；在0.2mg/kg/天及以上剂量组，观察到体重增加有减缓趋势。2. 在0.2mg/kg/天及以上剂量组，观察到淋巴细胞比例下降、谷草转氨酶（GOT）活性和碱性磷酸酶（A1P）水平升高；在0.8mg/kg/天剂量组，观察到游离脂肪酸升高。3. 在0.2mg/kg/天及以上剂量组，观察到束状带和网状带萎缩。在0.8mg/kg/天剂量组，观察到胸腺和肾上腺重量减轻，肝脏重量增加。4. 在恢复期结束时，除肾上腺和治疗部位外，大多数变化消失。从上述结果得出，在本研究条件下，若不考虑各组皮肤涂抹部位观察到的变化，雄性和雌性的毒理学无作用水平均为0.05mg/kg/天，明显中毒剂量水平为0.8mg/kg/天。
