CHARACTERIZATION OF A HISTAMINERGIC RESPONSE TO INTRAVENOUS CI-1010, A NITROIMIDAZOLE RADIOSENSITIZER, IN BEAGLE DOGS USING A CROSSOVER STUDY DESIGN

CI-1010, ethyl)amino]methyl]-2-nitro-1H-imidazole-1-ethanol monohydrob romide, a radiosensitizing anticancer agent, has both an affinity for hypoxic cells and an, alkylating functionality. Intravenous CI-1010 ca uses transient clinical signs in, dogs consistent with systemic histam ine release (erythema, urticaria, pruritus, hypotension, emesis). To c haracterize the response, six male and six female beagle dogs were giv en 10 mg/kg CI-1010 iv with or without antihistamine (AH) prophylaxis (diphenhydramine, 2.2 mg/kg im, bid; and cimetidine, 5 mg/kg im, tid) in a randomized crossover design. Plasma histamine levels were determi ned before and after dosing using a radioimmunoassay, and clinical sig ns were observed and/or scored. Analysis of the data established an ab sence of carryover effect between treatments. Plasma histamine Levels increased 95- to 339-fold following CI-1010 dosing, regardless of anti histamine pretreatment. Pretreatment with AH significantly reduced ery thema in males (p = 0.0001), with the difference approaching statistic al significance in females (p = 0.08). AH also moderated the degree of urticaria and the incidence of head rubbing or shaking, facial shin s welling, and vocalization. Using the crossover design, the number of a nimals required to meet the study's objectives was reduced.