聚乙二醇修饰的多柔比星脂质体在我国肿瘤患者体内的药动学研究

 目的 研究聚乙二醇修饰的多柔比星脂质体在我国肿瘤患者的药动学特征。方法 入选10名恶性肿瘤患者，聚乙二醇修饰的多柔比星脂质体（20~35 mg·m^-2）联合化疗给药后，采用HPLC测定给药后不同时间点的多柔比星血浆药物浓度，绘制血药浓度-时间曲线，以DAS软件拟合药动学模型，并得出聚乙二醇修饰的多柔比星脂质体的药动学参数，同时比较药动学参数在患者性别上的差异。结果 给药后0~168 h患者血药浓度为1.68~10.10 mg·L^-1， AUC _0-∞、CL、t1/2 、Vd等主要药动学参数值分别为（918.6±447.4） mg·h·L^-1、（0.037±0.02） L·h^-1·m^-2、（64.9±28.4） h、（2.95±0.88）L·m^-2。AUC_0-∞、CL、t1/2、Vd性别间无统计学差异。结论 聚乙二醇修饰的多柔比星脂质体在中国恶性肿瘤病人血浆中的药动学过程符合一室模型，半衰期长、清除率低、表观分布容积小。

Pharmacokinetics of Pegylated Liposomal Doxorubicin in Chinese Tumor Patients

OBJECTIVE To investigate the pharmacokinetics of pegylated liposomal doxorubicin(PLD) in Chinese tumor patients.METHODS Ten patients with malignant tumors were given PLD(20-35 mg·m-2) combined chemotherapy.Serial plasma samples were obtained after completion of the infusion.The doxorubicin concentrations in plasma were measured using high-performance liquid chromatography(HPLC).The pharmacokinetic parameters were estimated by DAS software.The correlations between those parameters and gender were analyzed.RESULTS The doxorubicin plasma concentration in the 10 patients ranged from 1.68 to 10.10 mg·L-1 during 0-168 h after administration.The AUC 0-∞,CL,t1/2 and Vd were(918.6±447.4)mg·L·h-1,(0.037±0.02) L·h·m-2,(64.9±28.4)h and(2.95±0.88)L·m-2,respectively.The differences of the pharmacokinetic parameters,ie AUC 0-∞,CL,t1/2 and Vd,between genders were not statistically significant.CONCLUSION The pharmacokinetics of PLD fits one-compartment model.with long retention time,low clearance and small volume of distribution.