紫杉醇在卵巢癌化疗患者中非线性药物动力学研究

Pharmacokinetics of paclitaxel in patients with advanced ovarian cancer

目的 通过对卵巢癌化疗患者的紫杉醇药物动力学研究 ,探讨紫杉醇的体内药物动力学特征。方法 本试验对 16名紫杉醇化疗患者进行了PK研究 ,患者的用药剂量分别为 135 ,175和 2 35mg·m- 2 ,输注 3h。输注过程及输注后 2 4h动态采集血浆标本 ,由HPLC测定血药浓度。采用PCNONLIN程序进行非房室模型参数计算和房室模型数据拟合。结果 紫杉醇代谢具有非线性特征 ,药物符合二室模型特点。本试验提示患者代谢能力低于国外文献报道 ,且在高剂量组的差别更为明显。结论 紫杉醇代谢个体差异较大 ,可能存在种族差别 ,有必要进行治疗药物监测 ,达到个体化治疗的目的。

OBJECTIVE To characterize the disposition of paclitaxel in patients with platinum pretreated ovarian carcinoma.METHODS Paclitaxel pharmacokinetics were studied in 16 patients with advanced ovarian cancer after the administration at 135,175 or 235 mg·m -2 by a 3 hour infusion schedule.Fourteen plasma samples were obtained during the infusion and up to 24 hours after the infusion.The concentrations of paclitaxel were determined by a reverse-phase high-performance liquid chromatography (HPLC).The pharmacokinetics was assessed by noncompartment and model-dependent methods.RESULTS Paclitaxel disposition was nonlinear after the 3 hour infusion.The plasma disposition of paclitaxel was consistent with a two-compartment pharmacokinetic model.Its metabolism in patients here appeared to be slower than that of other pharmacokinetic studies abroad.CONCLUSION There was variability of metabolism along patients.It strongly suggests to monitor paclitaxel in plasma at 24 hour post-administration.