Pharmacologic disposition of chlorozotocin in mice.

Cholorozotocin is a water-soluble chloroethylnitrosourea with the cytotoxic group attached to the C2 position of glucose. The distribution of the alkylating and carbamoylating moieties of the chlorozotocin molecule was determined in mice following the ip administration of an LD10 dose: 20 mg/kg. The half-life (T 0.5) for the plasma disappearance of intact drug was 5 minutes. The plasma disappearance of the ethyl-14C group was biphasic up to 120 minutes after administration; the T 0.5 of the initial phase was 17.5 minutes and the T 0.5 of the prolonged second phase was107 minutes. The disappearance of glucose-14C chlorozotocin followed kinetics similar to the chloroethyl-labeled compound. Fifteen minutes after administration, ethyl-14C drug concentrated maximally in the liver (194 nmols/g of tissue) and the kidney (131 nmols/g of tissue). Uptake into the bone marrow at 60 minutes after ip administration of the ethyl-labeled drug was 6.6 pmols of the ethyl-14C group covalently bound to proteins and nucleic acids per 10(7) nucleated cells. The concentration of ethyl-14C drug in the brain remained at 4 mnols/g of tissue up to 2 hours after administration, reflecting the water-soluble property of this new nitrosourea.