Rahmani R, Samak R, Bore P, Cano J P
INSERM U 278, Faculté de Pharmacie, Marseille, France.
Bull Cancer. 1988;75(2):195-200.
Vinca alkaloids (VA) represent a family of closely related molecules, which includes vincristine (VCR), vinblastine (VLB), vindesine (VDS) and navelbine (NVB), a new synthetic VA presently in phase II clinical trial. Development of sensitive and specific analytical tools (polyclonal and monoclonal antibodies) enabled us to investigate the kinetic behavior of VDS and NVB after IV bolus or long term administration. Following IV bolus injection, the mean pharmacokinetic parameters are: total plasma clearance: 0.53 l/h-1kg-1, 0.72 l/h-1kg-1 and apparent elimination half-life: 23.2 h, 39.5 h for VDS and NVB, respectively. Chronic treatment reveals time- and dose-dependence relationships and detailed observations of individual kinetics demonstrate an important interindividual variability for both drugs. Renal excretion of VDS and NVB is low (from 5 to 12% of the total dose), suggesting the important role of the liver in their rapid elimination.
长春花生物碱（VA）是一类密切相关的分子家族，其中包括长春新碱（VCR）、长春碱（VLB）、长春地辛（VDS）和长春瑞滨（NVB，一种目前正处于II期临床试验阶段的新型合成VA）。灵敏且特异的分析工具（多克隆抗体和单克隆抗体）的开发使我们能够研究VDS和NVB静脉推注或长期给药后的动力学行为。静脉推注后，平均药代动力学参数为：总血浆清除率：VDS为0.53升/小时·千克-1，NVB为0.72升/小时·千克-1；表观消除半衰期：VDS为23.2小时，NVB为39.5小时。长期治疗显示出时间和剂量依赖性关系，对个体动力学的详细观察表明这两种药物都存在重要的个体间差异。VDS和NVB的肾排泄率较低（占总剂量的5%至12%），这表明肝脏在它们的快速消除过程中起重要作用。
