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Carcinogenicity Studies of Astemizole in Mice and Rats

Janssen Research Foundation, Division of Janssen Pharmaceutica N.V., Turnhoutseweg 30, B-2340 Beerse, Belgium

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 doserelated 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.

¹ To whom requests for reprints should be addressed, at Department of Toxicology, Janssen Pharmaceutica, Turnhoutseweg 30, B-2340 Beerse, Belgium.

Received 7/ 5/95. Accepted 10/ 3/95.