ABSTRACT
Metronidazole derivative CMCa is a kind of radiosensitizers to tumor hypoxic cells. It can highly concentrated in cancer tissues. Acute toxicity assay revealed that ALD was 3.43 g/kg and MLD was 4.0g/kg. No significant changes in clinical symptoms, blood pictures and hepatorenal function were found at small dose (1g/kg), but at middle dose (2 g/kg) nausea and vomiting might occur but not significant in laboratory findings. However at larger dose (4.0 g/kg) the G-I and CNS symptoms were marked, and the cause of death was DIC. So, it can not be used in clinically at this dosage. Owing to the unstability of CMCa it should be prepared freshly before usage.
ABSTRACT
The blood radioactivity-time curve after iv [3H] CMCa in S180 bearing mice was found to be diexponential model.Pharmacokinetic parameters; t1/2 ?=9.6min, t1/2 P=37 h.It was quite rapidly distributed from the central compartment to the peripheral compartment.The highest radioactivity and the slowest metabolic rate were found in tumor.It further confirmed our foregoing result that this drug could concentrate in tumor,and was lower in brain with decreased neurotoxicity.The metabolic rates of the drug in blood and muscle were quite rapid, indicating it might be useful for clinical diagnosis and therapy of tumor.The results analyzed by TLC and scintillation counting of urine taken 24 h after iv [3H] CMCa to S180 bearing mice indicated that approximately 80% of urine total radioactivity was excreted as original drug in unchanged form and 7% as its hydrolyzate metronidazol.These results were similar to those in normal mice.