Castle M C, Margileth D A, Oliverio V T
Cancer Res. 1976 Oct;36(10):3684-9.
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.
研究了氚标记长春新碱在大鼠和犬体内的分布与排泄情况。在这两种动物中均发现药物从血液中消失呈现双相曲线，初始半衰期约为15分钟，次级半衰期约为75分钟。大鼠在1小时时组织水平较高，随后迅速下降，但脑部除外，在脑部任何时候药物水平都非常低。胆汁是主要排泄途径。发现胆汁中排泄的峰值速率在大鼠中（10分钟）比在犬中（60分钟）出现得更早。给予高剂量长春新碱（1.0毫克/千克）的大鼠比给予低剂量（0.1毫克/千克）的大鼠在胆汁中排泄的剂量百分比更高。给予低剂量长春新碱（0.1毫克/千克）的大鼠，超过85%的药物在72小时内通过粪便和尿液排泄。胆汁和尿液中总放射性的不到10%是代谢产物，而在血浆中，代谢产物占总放射性的40%。
