Distribution and excretion of (3H)vincristine in the rat and the dog

The distribution and excretion of tritiated vincristine were studies 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 in 1 hr in the rat and declined rapidly, except in the brain where very low levels of drug were found at all times. The bile was found to be the major route of excretion. The peak rate of excretion in bile was found to occur 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 the urine over 72 hr. 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.