两性霉素B脂质体注射剂与市售注射剂家兔体内药代动力学行为的比较

The pharmacokinetic characteristics of amphotericin B liposomes injection compared with market injection in rabbits after intravenous administration

目的 :比较自制的两性霉素B脂质体注射剂 (amphotericinBliposomes ,LAmB)和市售两性霉素B注射剂(marketamphotericinB ,MAmB)在家兔体内的药代动力学行为。 方法 :分别静脉注射单剂量 (1mg·kg-1)的LAmB和MAmB ,用HPLC法测定血浆中的药物浓度 ,用 3P97程序和Excel处理和分析数据 ,求算有关药代动力学参数。结果 :经 3P97程序拟合 ,家兔静脉注射单剂量LAmB和MAmB后其血药浓度 时间数据分别符合权重为 1/C和 1的三室模型 ;静脉注射LAmB和MAmB后Cmax分别为 (8.4± 2 .1)和 (2 .4± 0 .6 )mg·L-1,AUC分别为 (2 2 .5±6 .8)和 (9.0± 1.9)mg·h·L-1,CL分别为 (0 .0 5 0± 0 .0 2 4)和 (0 .114± 0 .0 2 2 )L·h-1,Vc 分别为 (0 .13± 0 .0 4)和(0 .46± 0 .18)L ,可见LAmB比MAmB注射后具有更高的血药浓度水平和更大的血药浓度 时间曲线下面积 ,以及较低的总体清除率和较小的表观分布容积。结论 :LAmB和MAmB在家兔体内的药代动力学行为有显著的不同 ,这些药代动力学特性的改变 。

To compare the pharmacokinetic characteristics of amphotericin B liposomes injection (LAmB) with market amphotericin B injection (MAmB) in rabbits by intravenous administration. Methods: LAmB and MAmB were intravenously administrated to rabbits at a single dosage of 1 mg·kg -1 . The AmB concentrations in plasma samples were determined by HPLC, and the pharmacokinetic parameters were calculated by means of 3P97, and ANOVA were done by means of the Excel software. Results: The concentration time data of LAmB and MAmB after intravenous administration were best fitted according to three compartment model with a weight of 1/C and 1 respectively . After a single intravenous administration, C max of LAmB and MAmB were 8.4±2.1 and 2.4±0.6 mg·L -1 , AUC were 22.5±6.8 and 9.0±1.9 mg·h·L -1 , CL were 0.050±0.024 and 0.114± 0.022 L·h -1 , V c were 0.13±0.04 and 0.46±0.18 L, respectively. Comparing with MAmB, all rabbits showed high plasma levels, large area under the curve values and low clearance, small apparent volume of distribution of LAmB. Conclusion: There were several striking differences between the pharmacokinetics properties of LAmB and MAmB injection in rabbits. All changes of the pharmacokinetics properties will be advantageous to reduce toxicity and improve therapeutic effect.