【摘要】 目的 :研究高剂量表阿霉素 (EPI)在肿瘤化疗患者体内的药物动力学过程 ,并初步探讨药效学特点。方法 :11例肿瘤患者接受了包含 10 0mg/m2 高剂量EPI的联合化疗 ,高效液相色谱法 (HPLC)测定血药浓度 ;PCNONLIN程序进行药动学房室模型数据拟合和参数计算 ;血液学毒性指标作为药效学参数 ,进行药动学和药效学相关性及剂量调整因素的研究。结果 :高剂量EPI的消除具有典型的三室特征 ,患者对EPI的代谢存在较大的个体差异 ;药效学和药动学参数之间未见到明显相关性 ,年龄与血浆清除率之间呈负相关。结论 :经与低剂量表阿霉素相比较 ,并未发现药物动力学参数的差异 ;年龄是影响清除率的一个重要因素 ,对高龄患者应适当减少药物剂量 ;应用 10 0mg/m2 EPI患者的耐受性良好。更多还原

【Abstract】 Objective:This study was designed to characterize the pharmacokinetics and pharmacodynamics of high dose epirubicin in cancer patients Methods:Eleven cancer patients were administered a dose of 100 mg/m 2 epirubicin The concentration of epirubicin in the blood were determined by high performance liquid chromatographic (HPLC)assay The modelling data were performed with a compartment pharmacokinetic modelling program (PCNONLIN) Hematological toxicity was used as the pharmacodynamic index The relationships between the pharmacokinetics and pharmacodynamics and other factors affecting dose modulation were assessed Results: The pharmacokinetics of high dose epirubicin was best described by a typical three compartment model It showed wide interindividual variation There was no correlation between its pharmacokinetics and pharmacodynamics Age was negatively correlated with epirubicin clearance Conclusions: There was no difference for the pharmacokinetic parameters between high dose and low dose Total clearance appears to be decreased with age and indicating that it is necessiary to reduce dose for the elderly patients Tolerance of the patients receiving a dose of 100 mg/m 2 epirubicin was good更多还原