甘氨双唑钠的Ⅰ期临床药代动力学(英文)

Phase Ⅰ clinical pharmacokinetics of glycididazolum natrium

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。

AIM To study the pharmacokinetics of a new radiosensitizing agent glycididazolum natrium (CMNa) in lung cancer patients after single and multiple dose administration. METHODS Twenty four cancer patients were for single dose study; and 5 patients were for multiple dose study. The CMNa and metronidazole concentrations in blood and urine were determined by HPLC with UV detector. The blood CMNa concentration time curves were simulated by 3P97 software and the pharmacokinetic parameters were calculated. RESULTS The blood CMNa concentration time curves in single dose groups were fitted to two compartment open model , t 1/2β were 0.76-2.62 h ,c max were 13.31-43.90 mg·L -1 , AUC were 8.68-29.94 mg·h·L -1 in 400, 500, 600, 700, 800 and 900 mg·m -2 dose groups, respectively and their c max and AUC were direct proportional to doses. The blood concentration time curves, pharmacokinetics parameters, and excretion ratios between single dose and multiple dose were similar, and there was no significant difference. CONCLUSION CMNa distributed and eliminated rapidly, so CMNa will not accumulate in patients′ bodies if it is administered at an appropriate interval.