Effect of Mannitol on the Toxicity of NSC-119,875 (cisplatin) Given as Weekly Intravenous Injections to Dogs for 14 Weeks

摘要

NSC-119,875 (cisplatin) was administered intravenously (i.v.) weekly for 14 weeks to 8 beagle dogs at a dose level of 0.5 mg/kg/week (10 mg/sq m/week). Four of these dogs were also given mannitol, initiated immediately after NSC-119,875 injection. Controls consisted of two dogs given 0.9% NaC1 on the same treatment schedule as NSC-119,875 and two dogs given 0.9% NaC1 followed by mannitol. Mannitol was administered as an i.v. infusion of 720 mg/sq m/week (36 mg/kg/week) of a 3 or 6% mannitol solution in a 6-hr period. The primary clinical signs of cisplatin toxicity were anorexia or decreased food intake, emesis, mucus in the feces, diarrhea and loose stool. These signs were observed with equal incidence and severity in nondiuresed and diuresed NSC-119,875 treated dogs. Hematologic changes included decreased leukocytes, reticulocytes, platelets, and relative number of lymphocytes. The most prominent blood chemistry changes were elevated BUN. This change was first noted in the latter half of the study period and became maximal during the last week of the treatment phase.