宫颈癌同等剂量卡铂不同方式动脉化疗中的临床药代动力学研究

Clinical pharmacokinetics of the same doses of carboplatin in different arterial chemotherapy ways for cervical cancer

目的研究同等剂量卡铂用于不同方式动脉化疗后,宫颈癌组织中卡铂的药代动力学变化及探讨新鲜明胶海绵颗粒的作用。方法选择经病理检查证实为宫颈癌,癌灶较大易于取材的患者18例,随机分为A组:卡铂400 mg/m^2双侧子宫动脉灌注后+新鲜明胶海绵颗粒栓塞;B组:卡铂300 mg/m^2双侧子宫动脉灌注后+(卡铂100 mg/m^2+新鲜明胶海绵颗粒混合)栓塞。总量为卡铂400 mg/m^2一次性给药。于灌注后0 h、0.17 h、0.33 h、0.5 h、1 h、7 h、13 h、25 h、49 h钳取宫颈癌组织,采用原子吸收光谱法测定其铂浓度,计算其药代动力学参数。结果 (1)A、B两组宫颈癌组织内铂离子平均药物浓度曲线均为双峰曲线,第一峰值均出现在灌注化疗后即刻,随着时间的延长呈快速下降趋势;第二峰值出现在栓塞化疗后即刻至6 h,随着时间的延长呈一缓慢下降曲线。(2)卡铂在宫颈癌组织中的变化符合非房室模型,A、B两组铂浓度峰值药物峰浓度、达峰时间、药时曲线下面积、半衰期、平均滞留时间、清除率、表观分布容积差异均无统计学意义。结论在宫颈癌动脉化疗中,同等剂量下调整卡铂动脉化疗给药方式的不同并不影响其在癌组织内吸收、分布、代谢及排泄过程,从而推测出新鲜明胶海绵颗粒不具有药物缓释作用。

Objective To observe the pharmacokinetics changes of the same doses of carboplatin in different arterial chemotherapy ways for cervical cancer and explore the effect of gelfoam particles. Methods Eighteen patients with locally advanced cervical cancer diagnosed by histopathology were randomly divided into two groups. Patients in group A were administered with carboplatin at the dosage of 400 mg/m2 by infusing, and then embolized with gelfoam particles （1mm in diameter）. Patients in group B were administered with carboplatin at the dosage of 300 mg/m2 by infusing, and then embolized with the mixture of carboplatin at the dosage of 100 mg/m2 and gelfoam particles （1mm in diameter）. Carboplatin was administered by infusing into two groups respectively at the dosage of 400 mg/m2. Tissues from the cervical cancer lesions were collected at different times （Oh, 0.17 h, 0.33 h, 0.5 h, 1 h, 7 h, 13 h, 25h and 49h after infusion） of two groups and then analyzed by using atomic absorption spectrometry and calculate their pharmacokinetic parameters. Results （ 1 ） The concentration-time curve of platinum in tumor tissues in two groups was of noncompartmental model. The peak value concentration of platinum in tumor tissues of the two groups were observed immediately after infusion, and then descended quickly. Another peak value of concentration of platinum in tumor tissue of two groups was observed between immediately and 6 hours after embolization and descended slowly. （2） there was no significant difference of Cmax, Tmax, AUC（0 - 49h）, tl/2, MRT, CL/F and Vd/F between the two groups. Conclusions In cervical cancer arterial chemotherapy, different arterial chemotherapy ways with the same dose of carboplatin does not affect the carboplatin’s absoiption, distribution, metabolism and excretion process, thus, gelfoam particles have no sustained-release effect.