DISTRIBUTION AND EXCRETION OF [VINCRISTINE-H-3] IN RAT AND DOG

Abstract

The distribution and excretion of the antitumor agent 3H-vincristine were studied in the rat and the dog. Biphasic curves for the disappearance of the drug from blood were found in both species, with an initial half-life of approximately 15 min and a secondary half-life of approximately 75 min. Tissue levels were high at 1 h in the rat and declined rapidly, except in the brain where low levels of drug were found at all times. The bile was the major route of excretion. The peak rate of excretion in bile occurred earlier in the rat (10 min) than in the dog (60 min). Rats given a higher dose of vincristine (1.0 mg/kg) excreted a larger percentage of the dose in the bile than rats given a lower dose (0.1 mg/kg). In rats given a low dose of vincristine (0.1 mg/kg), more than 85% of the drug was excreted in the feces and urine over 72 h. Less than 10% of the total radioactivity in the bile and urine was metabolites whereas, in the plasma, metabolites accounted for 40% of the total radioactivity.