Benze J, Gypen L, Vandenberghe J, Lampo A, De Coster R, Bowden C, Van Cauteren H
Janssen Research Foundation, Division of Janssen Pharmaceutica N.V., Beerse, Belgium.
Cancer Res. 1995 Dec 1;55(23):5589-94.
The histamine H1 antagonist astemizole (Hismanal) was tested for carcinogenicity in Swiss mice and Wistar rats. Astemizole was administered with the food to mice for 18 and to rats for 24 consecutive months. The doses given--approximately 5, 20, and 80 mg/kg body weight.day--were equivalent to 25, 100, and 400 times, respectively, the recommended human dose of 10 mg/day. Survival of both mice and rats was comparable between groups. Peto's age-adjusted, dose-related trend analysis for the tumor-bearing rats did not reveal a statistically significant difference for males or females. There was no evidence that astemizole led to an increased incidence of spontaneously or unusually occurring neoplastic lesions in either mice or rats. Special attention was given to the effect of astemizole on the progression of spontaneously occurring mammary gland adenomas and fibroadenomas. Peto's analysis applied to the number of female rats bearing these benign mammary gland tumors disclosed no statistically significant dose-related trend. There was no positive trend for the onset of this tumor type, and the median size of the tumor over time per rat was also not statistically significantly different in a comparison of the control group with each of the dosed groups. The findings from these carcinogenicity studies suggest that astemizole is not tumorigenic and that it does not promote tumor growth.
对组胺H1拮抗剂阿司咪唑（息斯敏）进行了瑞士小鼠和Wistar大鼠的致癌性试验。将阿司咪唑混入食物中连续喂给小鼠18个月、大鼠24个月。所给剂量——约5、20和80毫克/千克体重·天——分别相当于人类推荐日剂量10毫克的25倍、100倍和400倍。各组小鼠和大鼠的存活率相当。对患肿瘤大鼠进行的Peto年龄校正剂量相关趋势分析显示，雄性和雌性大鼠均无统计学显著差异。没有证据表明阿司咪唑会导致小鼠或大鼠自发或异常发生的肿瘤性病变发生率增加。特别关注了阿司咪唑对自发发生的乳腺腺瘤和纤维腺瘤进展的影响。应用于患有这些良性乳腺肿瘤的雌性大鼠数量的Peto分析未发现统计学显著的剂量相关趋势。这种肿瘤类型的发病没有正向趋势，并且在对照组与各给药组的比较中，每只大鼠随时间推移肿瘤的中位大小也没有统计学显著差异。这些致癌性研究结果表明，阿司咪唑不具有致瘤性，也不会促进肿瘤生长。
