【摘要】 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。更多还原

【Abstract】 Objective To make a research into the pharmacokinetics of tamoxifen at a high dosage for clinical use in NSCLC patients.Methods Three qualified NSCLC patients were selected to make TAM 160 mg per Os. Blood samples are collected at different times and then analyzed by HPLC.The parameters were got from the PK-GRAPH programe.60 qualified NSCLC patients were divided randomly into two groups: TAM+chemotherapy and chemotherapy.All the patients received treatment of two cycles and then the effect and the toxicity were detected.Chi-square test has been used for statistic analysis.Results The concentration-time courses of the TAM 160 mg was fitted to one-compartment model.The pharmacokinetic parameters were estimated as follows: T_max（6.3454±1.244 6） h C_max（217.385±7.705） ng/mL AUC（12 127.385±636.156 5） ng·h/mL T1/2ke（34.125 7±2.967 5） h.The effects of TAM and chemotherapy group（48%） are higher than those of chemotherapy group（13%）.（P<0.05,χ²=4.176）.Conclusion TAM 160 mg/d could not prove to reach the effective maintenance concentration in vivo that is required for reversing MDR in vitro.Loading-maintenance dose strategy has been recommended.The strategies of TAM+chemotherapy group TAM 320 mg 1 d,160 mg 2-7 d Per Os and chemotherapy improved effect.So this strategy is recommended for the further clinical trial.更多还原