国产紫杉醇对晚期卵巢癌患者腹腔化疗药代动力学的研究

The pharmacokinetic study on taxol for patients with advanced ovarian cancer.

目的：研究国产紫杉醇腹腔用药的药代动力学及其副作用。方法：对８例初治晚期卵巢上皮性癌应用国产紫杉醇１７５ｍｇ／ｍ２作腹腔化疗，３ｗ１次，观察副作用。对其中６例进行药代动力学研究，在用药前、后取腹水及血浆测定紫杉醇的药物浓度，测定药代动力学参数。结果：腹水中的药物浓度及浓度—时间曲线下面积远高于血浆中的相应情况。紫杉醇代谢模型为二室型，具有药代动力学优势。其副作用主要是骨髓抑制及腹痛，但较静脉用药的副作用小。结论：国产紫杉醇腹腔用药具有药代动力学优势，副作用小。

Objective: To evaluate safety and pharmacokinetics of the intraperitoneal(IP) administration of the antineoplastic agent taxol. Methods:Eight untreated patients with advanced epithelial ovarian cancer entered into a trial.Taxol dose was 175mg/m 2.Patients were treated with taxol administred IP every 3 weeks and side effects were observed.Six of eight entered onto the pharmacokinetics trial of taxol administred IP.The concentrations of taxol in ascites and plasma were measured before and after taxol administrated.Results:The concentration and the exposure of the peritoneal cavity(peak levels and area under the time versus concentration,AvsC)to taxol after IP delivery in ascites were more higher than those of the plasma.The elimination of taxol from the peritoneal compartment was described optimally by two compartments model and had major pharmacokinetic advantage for cavity exposure.The main toxicity phenomens were abdomen pain and leukopenia,but were less than intravenous therapy.Conclusion:Taxol can be delivered by the IP route with both an acceptable toxicity profile and has major pharmacokinetic advantage for cavity exposure.