摘要
目的 通过监测阿霉素 (ADM)的血药浓度 ,比较支气管动脉灌注与静脉全身化疗在药代动力学方面的差异。方法 (1)动物实验组 :家兔 2 4只 ,观察ADM单独用药或与DDP、MMC不同方式配伍时药代动力学参数的变化。 (2 )临床研究组 :原发性中心型肺癌 17例 ,采取联合用药 (ADM +DDP +MMC)支气管动脉灌注化疗。分别取动、静脉血 ,以荧光分光光度法测定血浆中阿霉素浓度。结果 线性范围在 10 1～ 10 6ng/ml内 ,r=0 .9983。日内标准误差 (s) <2 % ,日间s <3%。动物实验组单用ADM者血药浓度 时间方程为Cμg/ml=12 9.44e-13 .3 6t+0 .2 5e-0 .0 72t;三药配伍者为Cμg/ml=370 .93e-2 3 .4 3t+0 .0 4e-0 .0 9t。临床研究组动脉血样为Cμg/ml=44 8.6 1e-66.62t+16 .35e-8.13t;静脉血样为Cμg/ml=15 6 9e-2 1.66t+0 0 7e-0 .0 3 8t。结论 从药代动力学的角度衡量 ,ADM联合用药灌注化疗治疗支气管肺癌 ,是一种药效高、毒副作用低的治疗方法。
Objective This pharmacokinetic study was conducted to determine the plasma concentration of adriamycin after bronchial artery infusion (BAI), and to compare it with the conventional chemotherapy.Methods Twenty four healthy rabbits were devided into 4 groups with 6 animals in each. Comparison of the parameters was investigated in pharmacokinetics after ear lobe venous injection of ADM (Group 1) and in combination with DDP or/and MMC (Groups 2, 3, 4). Intracardial blood samples were obtained according to the fixed time and quantity. Dose for each drug was: ADM 2 mg/kg, DDP 4 mg/kg, and MMC 2 mg/kg. Seventeen patients suffering from primary non small cell bronchogenic carcinoma, the central type, confirmed by pathology and cytology comprised the clinical group, all of whom showing single blood supply by angiography, was given bronchial artery infusion. According to the scheduled time and quantity, we sampled blood species via indwelling catheter in the right median cubital vein after the bronchial artery infusion. Dose of the each drug was: ADM 40 mg/m 2, DDP 80 mg/m 2, and MMC 14 mg/m 2. Plasma concentration of ADM was determined by fluorophotometry. Since the cessation of chemotherapy, blood samples were taken from the thoracic aorta via indwelling catheter at 0, 1, 3, 5, 10, 15 and 20 minutes; venous blood samples were taken from the right cubital vein through the indwelling catheter at 0, 5, 10, 15, 20 minutes, and also at 0.5, 1, 2, 4, 8, 12, 24 and 48 hours altogether at 20 time spots with 2ml per sample. Results The calibration curve was linear from 10 ng/ml to 1 000 ng/ml with r =0.998 3. The relationship standard difference (RSD) within a day was lowered to 2%, and the RSD between days was lowered to 3%. The formula of concentration time curve for ADM was C μg/ml = 129.44e -13.36t + 0.25 e -0.072t in animal Group 1, and C μg/ml =370.93e -23.43t +0.04e -0.09t in Group 4 animal. The formula in the clinical group was C μg/ml (artery)=448.61e -66.62t +16.35e -8.13t (artery) and C μg/ml(vein) = 15.69e -21.66t +0.07e -0.038t (vein).Conclusion Compared with the conventional chemotherapy in pharmacokinetics, bronchial artery infusion can be used as a treatment for non small cell bronchogenic carcinoma with more effectiveness and less side effects. [
出处
《中华肿瘤杂志》
CAS
CSCD
北大核心
2001年第5期395-398,共4页
Chinese Journal of Oncology
基金
"九五"国家医学科技攻关资助项目 ( 96 90 7 0 3 0 7)
