替尼泊甙用于卵巢癌患者腹腔化疗的药代动力学研究  

A Pharmacokinetic Study of Teniposide in Intraperitoneal Chemotherapy of Ovarian Cancer

作　　者：陈爱平[1,2] 彭芝兰[1,2] 洪诤 林虹[1,2] 高国兰 姚国新[1,2] 邱方城 

机构地区：[1]华西医科大学附属第二医院妇产科 [2]湖北省十堰市人民医院

出　　处：《华西医科大学学报》1999年第1期95-97,100,共4页Journal of West China University of Medical Sciences

摘　　要：为探讨替尼泊甙（ＶＭ－２６）腹腔化疗的药代动力学特点及其毒副作用。用高效液相色谱法测定用药后腹水、血浆及尿液中ＶＭ－２６的浓度，比较三种剂量腹腔化疗的药动学参数。结果：ＶＭ－２６腹腔注药后，腹水及血浆中ＶＭ－２６的药物浓度－时间数据均符合二室药动学模型。腹水及血浆中的Ｃｍａｘ和ＡＵＣ均呈剂量依赖性，腹水中的Ｃｍａｘ和ＡＵＣ与血浆中的Ｃｍａｘ和ＡＵＣ之比分别为１３．４６±１．８９和７．６５±２．０３，腹腔与血浆的消除ｔ１／２分别为５．２８±０．９５和６．６４±２．７３。腹膜对药物的清除率为０．１９±０．０４，远低于机体对药物的总清除率１．３９±０．３１，尿２４小时，ＶＭ－２６的排泄率三种剂量组分别为用药总量的１１．１９±２．７６％、９．７５±２．５８％、１０．０２±１．２０％。ＶＭ－２６腹腔化疗对骨髓无抑制作用，消化道反应轻，仅有轻度腹痛。以上提示ＶＭ－２６用于卵巢癌患者腹腔化疗有较大的药动学优势，且毒副作用轻，有一定的临床应用前景。The objectives of this study were to determine the characteristics of pharmacokinetics of teniposide (VM 26) instilled intraperitoneally with three dosages (100 mg, 150 mg and 200 mg )and to evaluate its toxicity. Twelve patients with ovarian cancer were divided into three groups: teniposide 100mg IP, 5 pateints; teniposide 150mg IP, 5 patients; and teniposide 200mg IP, 2 patients. Samples of ascitic fluid, blood and urine were collected after administration of these drugs in 24 hours. Concentrations of teniposide were determined with high performance liquid chromatographic procedure. The results showed that the data collected from peritoneum and plasm were foundto conform to a two compartment open model. The peak concentration (Cmax) and the area under the curves (AUC) in peritoneal cavity and plasma were dose dependent. The ratios of Cmax and AUC between peritoneal fluid and plasma varied within 13.46±1.89 and 7.65±2.03 respectively. The elimination half lives (T 1/2β ) in the peritoneum and plasma of teniposide were 5.28±0.95 and 6.64±2.73 hours respectively. The volume of peritoneal distribution and its clearance were lower than those of plasma ( P<0.001 ). The side effects were mild and were not dependent on drug dosage. The results suggest that teniposide as an intraperitoneal therapeutic agent offers some advantages in the treatment of ovarian cancer. The tumor tissues and peritoneal growths could be bathed in a high concentration of teniposide. Teniposide is safe, reasonable in ntraperitoneal chemotherapy and shows prespects in the treatment of ovarian cancer.

关 键 词：替尼泊甙 药代动力学 卵巢肿瘤 药物疗法 

分 类 号：R737.310.5[医药卫生—肿瘤]