紫杉醇用于卵巢癌化疗的临床药效学研究

 目的:寻找紫杉醇药代动力学参数与疗效和毒性的关系?方法:10名卵巢癌化疗患者单独使用紫杉醇治疗,用药剂量为175mg·m^-2和235mg·m^-2?动态采集血样本,利用HPLC方法测定,计算药代动力学参数?记录用药过程中CA125改变和毒副作用?采用统计学方法和药代动力学模型进行分析?结果:c_max,AUC,AUMC和Cl与中性粒细胞减少症无关?而血浆浓度在0.1μmol·L^-1或0.05μmol·L^-1以上持续的时间与WBC减少百分数符合Sigmoid Emax模型?结论:在对此药的群体药代动力学特性深入研究后,监测给药后24h的血药浓度对临床合理用药具有积极意义?

Clinical Pharmacodynamics of Paclitaxel in Patients with Advanced Ovarian Cancer

OBJECTIVE:To define a pharmacodynamic relationships between paclitaxel disposition and its toxicity and efficacy after a 3 hour infusion.METHODS:Paclitaxel pharmacokinetics and pharmacodynamics were studied in 10 patients with advanced ovarian cancer.Paclitaxel was administered at 175mg·m^-2 or 235mg·m^-2 by a 3 hour infusion schedule. The changes of CA125 and adverse effects were obtained. The correlation of pharmacodynamics and pharmacokinetics were evaluated statistically by regression model.RESULTS: Investigation of pharmacodynamics showed no clear relationship between the pharmacokinetic parameters,AUC, c_max and toxicity. However , a relationship was found between the duration of plasma concentration above a threshold of 0.1μmol·L^-1(85.4ng·ml^-1) and the decrease of white blood cell count (WBC). CONCLUSION:It will be helpful to monitor the paclitaxel level at 24hr post-administration for limiting its adverse effects.