title: Cimetidine enhances cisplatin toxicity in mice.
abstract: The combination of the histamine H2 antagonist cimetidine (CMT) and the anticancer agent cisplatin (CDDP) was studied in normal and tumorbearing mice. CMT doses of 100 mg/kg produced no alteration in the survival of DBA/2J mice bearing P388 leukemia treated with CDDP doses of 3 mg/kg or 6 mg/kg. In these groups, the median survival was 13 days and 16 days, respectively, compared to 10 days in untreated controls. However, when adult CD-1 mice were given higher but nonlethal CDDP doses of 10, 15, or 18 mg/kg, the addition of CMT significantly increased CDDP lethality (P less than 0.05 by Wilcoxon analysis). For the 3 groups, CMT-enhanced lethality occurred in 10% of mice given 10 mg/kg CDDP, 80% of mice given 15 mg/kg, and 100% of mice given 18 mg/kg CDDP. Thus, CMT can acutely alter CDDP toxicity without affecting antitumor efficacy in mice.
authors.affiliation: Department of Internal Medicine, College of Medicine and Pharmacy, University of Arizona, Tucson.
authors.forename: R T
authors.initials: RT
authors.lastname: Dorr
authors.forename: M J
authors.initials: MJ
authors.lastname: Soble
mesh_terms: D000818:Animals; D002927:Cimetidine / Q000633:toxicity*; D002945:Cisplatin / Q000633:toxicity*; D004357:Drug Synergism; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA
chemical_list: D002927:Cimetidine; D002945:Cisplatin