紫杉醇治疗妇科恶性肿瘤的药代动力学与临床效果的关系研究

Association study between clinical pharmacokinetic of paclitaxel and chinical effect in patients with gynecological malignant tumor

目的:探讨紫杉醇治疗妇科恶性肿瘤的药代动力学与临床效果的关系。方法选取2009年1月~2013年12月期间开滦总医院收治的妇科恶性肿瘤患者78例,采用紫杉醇175 mg/m2静滴3 h,在化疗后不同时间采集血标本,测定血浆药物浓度,计算药代动力学参数,分析紫杉醇药代动力学与临床效果的关系。结果紫杉醇血浆药物峰浓度平均值为(3.99±1.07)mg/L,药物血浆浓度时间曲线下面积为(9.74±2.45)mg/(h·L),平均药物消除半衰期(13.7±3.2)h,平均表观分布容积(162.9±49.5)L/m2,平均清除率(8.2±1.0)L/(h·kg)。血药浓度-时间曲线符合二室模型;化疗有效者血药浓度>0.1μmol/L的持续时间(16.8±4.8)h大于化疗无效者(13.5±2.9)h,差异有统计学意义(P<0.05);出现严重不良反应者药物峰浓度(4.61±0.86)mg/L高于未出现严重不良反应者(3.65±1.13)mg/L,差异有统计学意义(P<0.01)。结论紫杉醇药物峰浓度与治疗后效果及严重不良反应相关。

Objective To observe the association between clinical pharmacokinetic of paclitaxel and adverse reactions in patients with gynecological malignant tumor.Methods 78 patients with female malignant tumor selected from Jan.2009 to Dec.2013 in Kailuan General Hospital were treated with paclitaxel (intravenous drip 175 mg/m2 3 h).The blood drug level of paclitaxel was measured at different time after treating.The DAS software was used to calculate the parameter of pharmacokinetic of paclitaxel,and the SPSS software was used to analyze the association between clinical pharmacokinetic of paclitaxel and adverse reaction in patients with female malignant tumor.Results The peak plasma concentrations (Cmax)was (3.99 ± 1.07)mg/L,the areas under the plasma concentration-time curve (AUC)was (9.74 ±2.45)mg/(h·L),the plasma elimination half-life (t1/2z)was (13.7 ±3.2)h,the apparent volumes of distribution (Vd)was (162.9 ±49.5)L/m2,the plasma clearance rates (CL)was (8.2 ±1.0)L/(h·kg).The kinetics of paclitaxel was fitted to two-compartment model.The time of drug concentration >0.1 μmol/L (t>0.1 )in responder patients (16.8 ± 4.8)h was higher than that in nonresponder patients (13.5 ±2.9)h,and the difference was significant (P<0.05).The Cmax in patients with severity adverse reactions (4.61 ±0.86)mg/L were higher than those in patients without severity adverse reaction (3.65 ±1.13)mg/L,and the difference was significant (P<0.01).Conclusion The Cmax of paclitaxel is associated with efficacy after treatment and severity adverse reactions.