Bender R A, Castle M C, Margileth D A, Oliverio V T
Clin Pharmacol Ther. 1977 Oct;22(4):430-5. doi: 10.1002/cpt1977224430.
The pharmacokinetics, metabolism, and excretion of aromatically labeled tritiated vincristine (VCR) was examined in 4 patients. Clearance of radioactivity from the blood was triphasic with half-life t1/2 values of 0.85, 7.4, and 164 min. The initial phases probably represent distribution and binding to formed blood elements which exceeded 50% of the administered dose by 20 min. Excretion of radioactivity was principally fecal, with 33% recovered in the feces by 24 hr and 69% by 72 hr. Considerably less radioactivity (12%) was excreted in the urine over the 72-hr period. Approximately 40% of fecally excreted and 46% of urinary excreted radiolabel represented metabolites, which suggests that at least 34% of the VCR dose was excreted as metabolies. Plasma metabolites represented from less than 1% to 30% or more of radioactivity in plasma. Ultraviolet spectral analysis of all metabolites revealed preservation of the intact VCR dimer, which suggests that metabolism involves alteration of side groups.
对4例患者研究了芳香族标记的氚化长春新碱（VCR）的药代动力学、代谢和排泄情况。血液中放射性的清除呈三相，半衰期t1/2值分别为0.85、7.4和164分钟。初始阶段可能代表分布以及与已形成的血液成分结合，在20分钟时超过给药剂量的50%。放射性排泄主要通过粪便，24小时时粪便中回收33%，72小时时回收69%。在72小时期间，尿液中排泄的放射性要少得多（12%）。粪便排泄的放射性标记物约40%以及尿液排泄的放射性标记物约46%为代谢产物，这表明至少34%的VCR剂量以代谢产物形式排泄。血浆代谢产物占血浆中放射性的不到1%至30%或更多。对所有代谢产物的紫外光谱分析显示完整的VCR二聚体得以保留，这表明代谢涉及侧链基团的改变。
