PHARMACOLOGIC DISPOSITION OF CHLOROZOTOCIN IN MICE

  • 1 January 1978
    • journal article
    • research article
    • Vol. 62  (8) , 1145-1151
Abstract
Chlorozoticin [an antineoplastic drug] 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 i.p. administration of an LD10 dose: 20 mg/kg. The half-life (T0.5) for the plasma disappearance of intact drug was 5 min. The plasma disappearance of the ethyl-14C group was biphasic up to 120 min after administration; the T05 of the initial phase was 17.5 min and the T0.5 of the prolonged 2nd phase was 107 min. The disappearance of glucose-14C chlorozotocin followed kinetics similar to the chloroethyl-labeled compound. Fifteen min. after administration, ethyl-14C drug concentrated maximally in the liver (194 nmol/g of tissue) and the kidney (131 nmol/g of tissue). Uptake into the bone marrow at 60 min after i.p. administration of the ethyl-labeled drug was 6.6 pmol of the ethyl-14C group covalently bound to proteins and nucleic acids per 107 nucleated cells. The concentration of ethyl-14C drug in the brain remained at 4 nmol/g of tissue up to 2 h after administration, reflecting the water-soluble property of this new nitrosourea.

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