Okazaki S, Nishimura S, Tamura K, Aikawa T, Hatayama K, Tanaka H, Tanaka G
Bozo Research Center Inc., Tokyo, Japan.
J Toxicol Sci. 1992 Nov;17 Suppl 3:91-122. doi: 10.2131/jts.17.supplementiii_91.
The toxicity of Prednisolone farnesylate (PNF) gel, a synthetic glucocorticoid, was investigated in the Sprague-Dawley rat. PNF gel was administered dermally to the rats at doses of 0.125, 0.5 and 2.0 mg/kg/day for 52 weeks, then the drug was withdrawn for 8 weeks to evaluate the reversibility. The results are summarized as follows: 1. In the PNF gel 2.0 mg/kg/day group, thinning of the skin at the application site, slightly retarded body weight gains, a tendency toward a decrease in the white blood cell count, an elevation of serum GOT and GPT activity, free fatty acid level, and a decrease in alpha 1-globulin fraction were observed. In the pathological examinations, decreased organ weights of the thymus, spleen and adrenal glands, and thinning of the skin were observed. Histopathological examination revealed atrophy of the thymus and zona fasciculata of the adrenal glands, thinning of the skin with atrophied skin appendages, and hepatocellular hypertrophy with hypertrophied uncleus in the perilobular zone. 2. In the PNF gel 0.5 mg/kg/day group, thinning of the skin at the application site and a decrease in alpha 1-globulin fraction were observed. Histopathologically, thinning of the skin atrophied skin appendages was observed. 3. In the PNF gel 0.125 mg/kg/day group, there were no toxic signs induced by the drug. 4. After the 8-week recovery period, the changes in the skin were observed in the 2.0 mg/kg/day group, but the severity was lowered. The other changes disappeared and so it was demonstrated that the changes were reversible. 5. Based on these results, it was concluded that the overt toxic dose of PNF gel was 0.5 mg/kg/day and the non-toxic dose was 0.125 mg/kg/day in the present study.
对合成糖皮质激素法尼酸泼尼松龙（PNF）凝胶进行了Sprague-Dawley大鼠的毒性研究。以0.125、0.5和2.0mg/kg/天的剂量对大鼠进行为期52周的经皮给药，然后停药8周以评估可逆性。结果总结如下：1. 在PNF凝胶2.0mg/kg/天组中，观察到给药部位皮肤变薄、体重增加略有迟缓、白细胞计数有下降趋势、血清谷草转氨酶（GOT）和谷丙转氨酶（GPT）活性升高、游离脂肪酸水平升高以及α1球蛋白组分降低。病理检查发现胸腺、脾脏和肾上腺的器官重量减轻，皮肤变薄。组织病理学检查显示胸腺萎缩、肾上腺束状带萎缩、皮肤及其附属器变薄以及小叶周围区肝细胞肥大且细胞核增大。2. 在PNF凝胶0.5mg/kg/天组中，观察到给药部位皮肤变薄以及α1球蛋白组分降低。组织病理学检查发现皮肤及其附属器变薄。3. 在PNF凝胶0.125mg/kg/天组中，未观察到该药物引起的毒性体征。4. 在8周恢复期后，2.0mg/kg/天组观察到皮肤有变化，但严重程度降低。其他变化消失，因此证明这些变化是可逆的。5. 根据这些结果得出结论，在本研究中，PNF凝胶的明显毒性剂量为0.5mg/kg/天，无毒剂量为0.125mg/kg/天。
