Prevention of radiation emesis in dogs by combinations of drugs.

Male mixed-breed dogs were used to evaluate the effectiveness of cimetidine (Cim), promethazine (Pro), and thiethylperazine (Thi), singly and in combination, to raise the threshold for radiation-induced emesis. Cim was chosen as an H2 antihistamine, Pro as an H1 antihistamine, and Thi as a phenothiazine derivative dopamine blocker. Doses were: 167 mg/m2 i.v. for Cim; 13.9 mg/m2 i.m. for Pro; and 5.6 mg/m2 i.m. for Thi. These doses were calculated on a mg/m2 basis to approximate doses for an average human (1.8 m2) of 300 mg Cim, 25 mg Pro, and 10 mg Thi. Exposure was to 60Co at 60 rad (midline) per min. The dogs were fed 0.4 kg canned dog food 1 hour before exposure, and injected with the appropriate drugs 30 minutes prior to exposure. Emesis onset times, number of episodes, and time to last episode were recorded. The radiation dose (midline tissue rad) to cause a 50% incidence of emesis (ED50) was calculated using an up-and-down procedure. The ED50 (95% confidence limits) were: 258 (212-315) for controls; 240 (151-380) for Cim; 313 (256-384) for Pro; 405 (319-514) for Thi; 334 (284-394) for Cim + Pro; 446 (365-546) for Cim + Thi; 347 (306-399) for Pro + Thi; and 478 (428-539) for Cim + Pro + Thi.