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目的进行大剂量的TAM 160 mg在肺癌患者体内的药物代谢动力学研究,为临床合理用药提供理论依据。方法选择符合条件的非小细胞肺癌患者3例,单次服用TAM 160 mg,在不同时间采集血样,进行高效液相色谱分析,采用PK-GRAPH程序求得参数。选择符合条件的非小细胞肺癌患者60例,随机分为TAM+化疗组及化疗组,进行2周期治疗后评价疗效和毒性,χ2检验比较显著性差异。结果TAM 160 mg血药浓度-时间曲线符合一房室模型,主要药代动力学参数为Tmax(6.3454±1.244 6)hCmax(217.385±7.705)ng/mL AUC(12 127.385±636.156 5)ng.h/mL T1/2ke(34.125 7±2.9675)h。TAM+化疗组有效率(48%)较化疗组(13%)高(P<0.05,χ2=4.176)。结论TAM 160 mg 1 d给药,不能达到体外逆转所要求的体内有效维持浓度,可采用负荷-维持给药法。继续进行大剂量三苯氧胺在肺癌患者体内的药物效应动力学研究。TAM+化疗组TAM 320 mg/dL,160 mg,2~7 d给药合并化疗提高了疗效,患者可耐受,推荐进行更大规模的临床试验。
Objective To study the pharmacokinetics of high dose TAM 160 mg in patients with lung cancer and provide a theoretical basis for rational clinical use. Methods Three patients with non-small cell lung cancer (NSCLC) were enrolled in this study. TAM 160 mg was given in a single dose. Blood samples were taken at different times and analyzed by high performance liquid chromatography (HPLC). PK-GRAPH program was used to determine the parameters. Sixty patients with non-small cell lung cancer (NSCLC) who were eligible were randomly divided into TAM + chemotherapy group and chemotherapy group. After two cycles of treatment, the curative effect and toxicity were evaluated. There was significant difference between the two groups in Chi-square test. Results The TAM 160 mg concentration-time curve fitted one-compartment model and the main pharmacokinetic parameters were Tmax (6.3454 ± 1.244 6) hCmax (217.385 ± 7.705) ng / mL AUC (12 127.385 ± 636.156 5) ng.h / mL T1 / 2ke (34.125 7 ± 2.9675) h. The effective rate of TAM + chemotherapy group (48%) was higher than that of chemotherapy group (13%) (P <0.05, χ2 = 4.176). Conclusion TAM 160 mg administered for 1 day can not achieve the effective in vivo maintenance concentration required for in vitro reversal, and the load-maintenance administration method can be adopted. Continue to carry out large doses of tamoxifen in patients with lung cancer drug effect kinetics. TAM + chemotherapy group TAM 320 mg / dL, 160 mg, 2 ~ 7 d combined with chemotherapy to improve the efficacy of patients with tolerance, recommended for larger clinical trials.