TUMORIGENICITY ASSAYS OF SOTALOL HYDROCHLORIDE IN RATS AND MICE

The Food and Drug Administration (FDA) has classed beta-adrenergic blocking agents as suspect for carcinogenicity regardless of their chemical structure. In response to this classification, two tumorigenicity bioassays as required by the FDA have been carried out with sotalol HCl. Mice were dosed with 300 or 600 mg/kg sotalol HCl or 100 mg/kg propranolol HCl mixed in the diet for 78 weeks. After three months of feeding drug-free diet, the mice were sacrificed, and the number and types of cancers occurring in each treated group were compared with a concurrent control group. There were no indications that either agent caused a change in the type or frequency of tumors. In a similar study with rats, dosages of 137 or 275 mg/kg sotalol HCl or 37.5 mg/kg propranolol HCl were administered for 78 weeks. All surviving rats were sacrificed at the end of two years. The types and prevalence of tumors in rats dying while on study and those sacrificed on schedule were similar for treated and control groups. The bioavailability of sotalol from the diets was demonstrated by the achievement of detectable, dose-related quantities in the blood of rats under similar conditions. The sensitivity to a known carcinogen of mice and rats of the strains used was also demonstrated. Groups of mice and rats of the same strains and sources were fed diets containing 0.03% 2-acetylaminofluorene. Both species developed tumors as a result of administration of this carcinogen.