Owellen R J, Hartke C A
Cancer Res. 1975 Apr;35(4):975-80.
Vinblastine, labeled with tritium in the 4-acetyl group, was given to two patients with malignant disease, and the pharmacokinetic behavior of the drug was determined. Clearance of radioactivity from the blood was biphasic, with t1/2 values for a first rapid phase of 4.25 and 4.78 min, and for a slower phase of 185 and 195 min. The volume of the central compartment was calculated as 29.7 and 39.4 liters, while the total fictive volume of distribution was 86.4 and 111.4 liters. Binding to blood components occurred in the order: plasma greater than platelets greater than red blood cells greater than white blood cells. Excretion of radiolabel occurred via the stool and the urine so that, after 72 hr, 25 and 41% of the total dose had appeared in the former and 19 a nd 23% had appeared in the latter. Appreciable amounts of unchanged drug appeared in the urine, while very little appeared in the stool, suggesting hepatic metabolism, consistent with prior animal studies.
将4-乙酰基用氚标记的长春碱给予两名恶性疾病患者，并测定该药物的药代动力学行为。血液中放射性的清除呈双相，第一个快速相的t1/2值分别为4.25分钟和4.78分钟，较慢相的t1/2值分别为185分钟和195分钟。中央室的容积计算为29.7升和39.4升，而总虚拟分布容积为86.4升和111.4升。与血液成分的结合顺序为：血浆＞血小板＞红细胞＞白细胞。放射性标记物通过粪便和尿液排泄，因此，72小时后，总剂量的25%和41%出现在粪便中，19%和23%出现在尿液中。尿液中出现了相当数量的未变化药物，而粪便中出现的很少，提示有肝脏代谢，这与先前的动物研究一致。
