Cataracts in beagle dogs given diazoxide

In two studies for toxicity, cataracts occurred in beagle dogs given diazoxide daily in high doses. Two of eighteen dogs given diazoxide intravenously at doses of 30.0 mg. per kilogram twice a day for fourteen days had reversible lenticular changes. These changes were not observed in dogs given 22.5 or 10.0 mg. per kilogram twice a day. By fifty-eight days after the last treatment, the cataracts had regressed or disappeared completely. In a study of diazoxide given orally for a maximum of seventy-eight weeks, cataracts developed in six of forty-two dogs given doses ranging from 50 to 200 mg. per kilogram daily, but none occurred in dogs receiving 15 or 30 mg. per kilogram daily. Hyperglycemia was observed at doses of 50 mg. per kilogram or higher. In five of the six dogs that had cataracts and hyperglycemia, vacuolation or absence of islet cells was seen on histologic examination of pancreatic tissue at necropsy. Ocular changes were attributed to the hyperglycemic effect of high doses of diazoxide given daily for prolonged periods. The daily doses given dogs in which cataracts developed were from ten to forty times that suggested in man (5 mg./kg.).