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目的 对一类新药肿瘤放射增敏剂甘氨双唑钠 (CMNa)进行单剂量和多剂量Ⅰ期临床药代动力学研究 ,对其吸收、分布、代谢、排泄及CMNa在体内的蓄积性作一评价。方法 6个单剂量组有 2 4名肿瘤病人 ,5名肿瘤病人受试者参与多剂量研究 ;采用高效液相 二极管阵列色谱法测定肿瘤放疗增敏剂CMNa及其代谢产物甲硝唑的血药浓度和尿药浓度 ,用 3P97软件对各单剂量组和多剂量组的血药浓度 时间曲线拟合 ,并计算药代动力学参数。结果6个单剂量组和多剂量组的CMNa血药浓度 时间曲线经拟合均符合开放型二室模型 ,4 0 0 ,5 0 0 ,6 0 0 ,70 0 ,80 0和 90 0mg·m- 2 组的主要药代动力学参数t1/ 2 β为 0 .76～ 2 .6 2h ,cmax为 13.31～ 4 3.90mg·L- 1,AUC为 8.6 8～ 2 9.94mg·h·L- 1,且单剂量组的cmax及AUC与剂量成正比。 70 0mg·m- 2 单次给药和连续 9次给药的多剂量组的肿瘤病人血药浓度 时间曲线几乎相吻合 ,各药代动力学参数值和排泄率没有统计学差异。结论 CMNa在肿瘤病人体内分布和消除均很快 ,一定间隔服用不会在病人体内蓄积 ,是一个较安全的放射增敏药物。
OBJECTIVE: To study single-dose and multiple-dose clinical pharmacokinetics of a new class of tumor radiosensitizer sodium glycididazole (CMNa). The absorption, distribution, metabolism, excretion and accumulation of CMNa in the body A comment. Methods Twenty-four tumor patients in six single-dose groups and five tumor patients were involved in the multi-dose study. The plasma concentrations of CMNa and its metabolite metronidazole were determined by high performance liquid chromatography with diode array. Concentration and urinary concentration, using 3P97 software on each single dose group and multiple dose plasma concentration time curve fitting, and calculate the pharmacokinetic parameters. Results The curves of CMNa concentration in six single-dose and multi-dose groups were fitted to the open two-compartment model at 4 0 0, 5 0 0, 6 0 0, 70 0, 80 0 and 90 0 mg · m - The main pharmacokinetic parameters t1 / 2 β of the two groups were 0.76 ~ 2.62h, cmax was 13.31 ~ 4 3.90mg · L- 1, AUC was 8.68 ~ 29.94mg · h · L -1 , And the single dose group of cmax and AUC is proportional to the dose. The time curve of plasma concentration of tumor patients with single dose of 70 0 mg · m-2 and multiple dose of 9 consecutive doses almost coincided, and the pharmacokinetic parameters and excretion rate of each dose had no statistical difference. Conclusion The distribution and elimination of CMNa in patients with tumors are fast, taking a certain interval will not accumulate in the patient’s body, is a safer radiosensitization drug.