Distribution and metabolism of vincristine in mice, rats, dogs, and monkeys.
An extraction procedure that allows measurement of [3H]vincristine and its metabolites in biologic fluids and tissues has been developed and used to determine the distribution and metabolism of vincristine in mice, rats, dogs, and monkeys. Very little tritium exchange occurred during the experiments. In mice and rats injected ip with [3H]vincristine, the peak serum levels of drug were reached at 15 minutes. For both mice and rats, the concentration of vincristine metabolites rose in the serum for 30 minutes, then remained high through 3 hours. For dogs and monkeys given an iv dose of [3H]vincristine, the initial serum levels fell rapidly, with half-lives for the first phase of 6 and 10 minutes respectively. The half-life for both of the second phases was 190 minutes. For both species, the serum level of metabolites fell for 2 hours, then remained relatively constant. These results were not appreciably altered when the animals were injected simultaneously with prednisone. Compared to serum levels in mice, rats, dogs, and monkeys, there was a marked accumulation of [3H]vincristine in all tissues examined, except the brain. The pancreas, spleen, kidneys, lungs, and liver of dogs and monkeys contained the largest amounts. The tissue distribution was not greatly different in dogs and monkeys injected simultaneously with prednisone. Urinary excretion of intact vincristine and its metabolites was observed for all four species. Both vincristine and its metabolites appeared in the bile of dogs and monkeys.
D000818:Animals; D001682:Biological Availability; D001921:Brain / Q000378:metabolism; D004285:Dogs; D005260:Female; D006207:Half-Life; D000882:Haplorhini; D066298:In Vitro Techniques; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008253:Macaca mulatta; D008297:Male; D051379:Mice; D051381:Rats; D013154:Spleen / Q000378:metabolism; D013997:Time Factors; D014316:Tritium; D014750:Vincristine / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism*
D014316:Tritium; D014750:Vincristine