TOXICITY TESTING OF ANTIMALARIAL DRUGS IN SWINE AND DOGS.

Abstract : Acute, subacute, and chronic toxicity studies and photosensitization studies were conducted in swine and dogs using antimalarial compounds singularly or in combination. The subcutaneous administration of WR-9838-B, 5 mg/kg or 10 mg/kg, for 15 consecutive days resulted in clinical manifestations of lameness, loss of weight and appetite, ocular involvement and swelling at injection sites. The oral administration of WR 40,070 for 28 consecutive days resulted in clinical manifestations of vomition, excessive salivation and hyperirritability. Healthy purebred beagle dogs were given a combination of chloroquine and trimethoprim orally in an 'Acute Minimum Lethal Dose Study' and in a 'Subacute Toxicity Study.' The symptoms observed included emesis, depression, incoordination, ataxia, convulsions and death. The minimum amount of the following antimalarial compounds required to consistently produce phototoxicity in white swine, when four doses were administered orally during 44 hours of U.V. light exposure was: quinine sulfate, 25 mg/kg; WR-7930, 15 mg/kg; and WR-30090, 25 mg/kg. Specific-pathogen-free swine were given a combination of chloroquine, primaquine, and D.F.D. orally, twice weekly for four weeks.