Schneck D, Butler F, Dugan W, Littrell D, Petersen B, Bowsher R, DeLong A, Dorrbecker S
Lilly Laboratories for Clinical Research, Eli Lilly Co., Indianapolis, IN.
Clin Pharmacol Ther. 1990 Jan;47(1):36-41. doi: 10.1038/clpt.1990.5.
The pharmacokinetics of a murine monoclonal antibody vinca conjugate (KS1/4-DAVLB) was investigated in 13 patients with adenocarcinomas who received single intravenous doses ranging from 40 to 250 mg/m2 and in three patients who were administered 1.5 mg/kg every 48 to 72 hours for up to 15 doses. Five patients in the single-dose study also received 100 microCi of [3H]-KS1/4-DAVLB. Overall mean values for the pharmacokinetic variables were as follows: elimination half-life, 31.5 hours; distribution volume, 4.43 L; and clearance, 0.09 L/hr. KS1/4-DAVLB demonstrated linear elimination kinetics in both the single- and multiple-dose studies. Significant concentrations of KS1/4-DAVLB were noted in a pleural effusion. Ten percent of the radioactive dose was recovered in the urine and 20% in the feces over a 5-day period. Small molecular weight vinca species were detected in the feces but not in the serum.
在13例腺癌患者中研究了鼠单克隆抗体长春花共轭物（KS1/4-DAVLB）的药代动力学，这些患者接受了40至250mg/m²的单次静脉注射剂量，另外3例患者每48至72小时接受1.5mg/kg的剂量，共给药15次。单剂量研究中的5例患者还接受了100微居里的[³H]-KS1/4-DAVLB。药代动力学变量的总体平均值如下：消除半衰期为31.5小时；分布容积为4.43升；清除率为0.09升/小时。在单剂量和多剂量研究中，KS1/4-DAVLB均表现出线性消除动力学。在胸腔积液中发现了显著浓度的KS1/4-DAVLB。在5天内，10%的放射性剂量从尿液中回收，20%从粪便中回收。在粪便中检测到小分子长春花物质，但在血清中未检测到。
