卡铂经不同给药方式后在家犬体内药物浓度的实验研究

Experimental study of platinum concentration in the blood of dogs via different administration of carboplatin

目的研究卡铂经静脉,动脉及腹膜后三种不同途径给药后,药物在动物体内的药代动力学情况。方法随机将18只雌性家犬分为3组,分别经静脉,动脉及腹膜后推注卡铂(16.5 mg/kg),然后于给药后的0、5、15分钟,0.5、1、2、4、8、24、72小时取静脉血,用高效液相色谱法(HPLC)测定血浆活性铂的浓度,计算和比较不同给药方式下卡铂的药代动力学参数。结果卡铂经静脉给药组血浆药物浓度峰值出现在给药结束即刻,动脉和腹膜后给药组血药浓度峰值出现在给药后15分钟。静脉给药组的血药浓度最大值达(218.20±37.20)mg/L,显著高于动脉给药组[(77.1±34.2)mg/L]及腹膜后给药组[(35.80±21.40)mg/L](P=0.001);静脉、动脉及腹膜后给药组的药时曲线下面积(AUC)分别为每小时(304.80±24.30)mg/L,每小时(228.10±74.00)mg/L和每小时(194.50±79.30)mg/L(P=0.0001)。动脉给药组和腹膜后给药组的表观分布容积基本相同,均大于静脉化疗组(P=0.015);三组间的清除率(CL)差异无统计学意义(P=0.832)。结论卡铂经不同途径给药的药代动力学参数存在显著差异。提示卡铂经动脉给药和经腹膜后给药后药物在体内组织分布可能更广泛,药物进入组织中的量也可能较静脉给药为多。

Objective To investigate the pharmacokinetics in plasma of the dogs after intravenous,intra-arterial and retroperitoneal carboplatin. Methods Eighteen female dogs were randomly divided into three groups. The dogs were administrated with earboplatin at the dosage of 16.5 mg/kg intravenously,intra-arterlally or retroperltoneally. The blood samples were taken at 0, 5, 15 minutes, and 0. 5, 1,2, 4, 8, 24 and 72 hours after instillation. The competent platinum concentrations were measured with high-performance liquid chromatography （HPLC）. Then the pharmacokinetie parameters were calculated and analysed. Results The peak concentration of platinum in the plasma reached instantly after instillation in the intravenous （IV） group,and at 15 minutes in the intra-arterial （IA） group and the retroperitoneal （RP） group. The maximal plasmie concentration （Cmax）of platinum was （218.20± 37.20） mg/L in IV group, which was significantly higher than that in IA [（77. 1±34. 2）mg/L] group and RP group r（35.80-k21.40）mg/L]（P=0. 001）. The area under the plasmic concentration-time curve （AUC） was [（304. 80±24. 30）mg/（L·h）] in IV group, [（228. 10±74. 00）mg/（L ·h）] in ]A group and [（194.50±79.30）mg/（L· h）] in RP groups,respectively（P=0. 0001）. The volume of distrihution（Vd）in IA and RP groups was almost the same,which was higher than that of the IV group（P= 0. 015）. There were no significant differences for the clearance（CL） among the three groups（P=0. 832）. Conclusions The pharmacokinetic parameters were significantly different among three groups. The results imply that the amounts and distributions of platinum in tissues by retroperitoneal and intra-arterlal carboplatin are more extensive than those by intravenous administration.