Optimal treatment schedule and antitumor spectrum of 4-carbamoylimidazolium 5-olate (SM-108) in murine tumors.
By designing optimal administration schedules, it was found that 4-carbamoylimidazolium 5-olate (SM-108) showed an excellent antitumor potency against a number of murine tumors. The optimal administration schedule of SM-108 was an intermittent multiple administration, in which the drug was multiply administered to mice at definite intervals of less than 3 hr for about 1 day on Days 1, 5, and 9 following tumor implantation. Although usual daily administration of SM-108 exhibited poor efficacy, the intermittent multiple administration of SM-108 exhibited potent antitumor activity against a wide variety of tumors, such as Ehrlich carcinoma, P388, 6-mercaptopurine-sensitive and -resistant L1210, Lewis lung carcinoma, Colon 26 adenocarcinoma, and Sarcoma 180. Among them, Ehrlich carcinoma showed the most prominent susceptibility to SM-108. With the intermittent multiple administration of SM-108, complete suppression was obtained in both the ascitic and solid forms of this tumor over a wide dose range. The schedule dependency of the antitumor effect of SM-108 described above was reasonably explained by its in vitro growth-inhibitory effects and pharmacokinetics in the mice.
D000818:Animals; D002286:Carcinoma, Ehrlich Tumor / Q000188:drug therapy; D003110:Colonic Neoplasms / Q000188:drug therapy; D004334:Drug Administration Schedule; D004353:Drug Evaluation, Preclinical; D007093:Imidazoles / Q000008:administration & dosage* / Q000627:therapeutic use; D007939:Leukemia L1210 / Q000188:drug therapy; D007941:Leukemia P388 / Q000188:drug therapy; D051379:Mice; D009374:Neoplasms, Experimental / Q000188:drug therapy*; D012510:Sarcoma 180 / Q000188:drug therapy
D007093:Imidazoles; C033758:4-carbamoylimidazolium 5-olate