Okazaki S, Yamazaki E, Tamura K, Hoshiya T, Anabuki K, Tanaka H, Tanaka G
Bozo Research Center Inc., Tokyo, Japan.
J Toxicol Sci. 1992 Nov;17 Suppl 3:49-89. doi: 10.2131/jts.17.supplementiii_49.
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 PNF gel was administered dermally to the rats at doses of 0.25, 1, 4 and 16 mg/kg/day for 13 weeks, then the drug was withdrawn for 5 weeks to evaluate the reversibility. In addition, 10 mg/kg/day prednisolone gel (PN gel), which is approximate to 16 mg/kg/day PNF gel in prednisolone molarity, was also administered to the rats for comparison. The results are summarized as follows: 1. In the PNF gel 16 mg/kg/day group, temporary erythema at the application site, retarded body weight gains, a decrease in the white blood cell count and lymphocyte ratio with an increase in the segmented neutrophil ratio, an elevation of serum AIP activity were observed. The pathological examinations revealed atrophy of the adrenal glands, lymphatic organs and skin. In addition, histopathological lesions were also found in the liver, pancreatic islets, bone, bone marrow and mammary glands. 2. In the PNF gel 4 mg/kg/day group, retarded body weight gains were observed, and histopathological lesions were noted in the adrenal glands, lymphatic organs, skin at the application site, liver and bone marrows. 3. In the groups that received less than 1 mg/kg/day of PNF gel, there were no toxic signs induced by the drug. 4. In the PN gel 10 mg/kg/day group, drug-related changes were almost similar to those of the PNF gel group, but the severity of the lesions was stronger than in the PNF gel group. 5. After the 5-week recovery period, the above changes almost completely disappeared and so it was demonstrated that the changes were reversible. 6. Based on these results, it was concluded that the overt toxic dose of PNF gel was 4 mg/kg/day and the non-toxic dose was 1 mg/kg/day in the present study.
研究了合成糖皮质激素法尼醇泼尼松龙（PNF）凝胶在Sprague-Dawley大鼠中的毒性。以0.25、1、4和16mg/kg/天的剂量对大鼠进行13周的皮肤给药，然后停药5周以评估可逆性。此外，还以10mg/kg/天的泼尼松龙凝胶（PN凝胶，其泼尼松龙摩尔浓度与16mg/kg/天的PNF凝胶近似）对大鼠给药以作比较。结果总结如下：1. 在PNF凝胶16mg/kg/天组，观察到给药部位出现暂时性红斑、体重增加迟缓、白细胞计数和淋巴细胞比例降低以及分叶中性粒细胞比例增加、血清碱性磷酸酶（AIP）活性升高。病理检查显示肾上腺、淋巴器官和皮肤萎缩。此外，在肝脏、胰岛、骨骼、骨髓和乳腺中也发现了组织病理学病变。2. 在PNF凝胶4mg/kg/天组，观察到体重增加迟缓，并且在肾上腺、淋巴器官、给药部位的皮肤、肝脏和骨髓中发现了组织病理学病变。3. 在接受低于1mg/kg/天PNF凝胶的组中，未观察到该药物诱导的毒性迹象。4. 在PN凝胶10mg/kg/天组，与药物相关的变化几乎与PNF凝胶组相似，但病变严重程度比PNF凝胶组更强。5. 在5周的恢复期后，上述变化几乎完全消失，因此证明这些变化是可逆的。6. 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4mg/kg/天，无毒剂量为1mg/kg/天。
