绿原酸联用阿霉素犬的药物动力学研究

Pharmacokinetics effect of Adriamycin by chlorogenic acid in Beagle dog

目的研究给予Beagle犬绿原酸和阿霉素后犬体内阿霉素的药物物动力学规律。方法 Beagle犬被随机分为阿霉素组和联合用药组。静脉给药后采集血样,制备血清,以HPLC法测定血药浓度。色谱柱为Aichrombond-AQC18(150mm×4.6mm,5μm),流动相为0.01mol·L-1KH2PO4-甲醇-乙腈-甲酸(50∶40∶10∶0.1),流速1.0mL·min-1,波长254nm。结果阿霉素0.011～11.4μg·mL-1(r=0.9990)与峰面积的线性关系良好,最低检测浓度为5.25ng·mL-1。联合用药前后阿霉素均呈二室模型;Cmax为0.457、0.557mg·L-1,Tmax为15、15min,T1/2为18.70、22.79min,Cl为0.029、0.027L·min-1·kg-1,AUC为54.99、59.53mg·L-1·min-1,相对生物利用度为115.40%。结论联合用药后,绿原酸对阿霉素的药物动力学模型无显著影响,但阿霉素清除率略有下降,半衰期及AUC增加,生物利用度明显提高(P<0.05)。绿原酸与阿霉素联合用药,可提高阿霉素的治疗浓度,且半衰期略有增长。

OBJECTIVE To investigate the interactive effects between Adriamycin( AMD) and chlorogenic acid ( CHA) in Beagle dog,the pharmacokinetics of AMD before and after the drug combination injection administration were studied. METHODS Beagles as the subjects were random by divided two groups,one was the combination administration group,the other was AMD only administration group. The drug serum concentration was determined by HPLC. RESULTS The linear range of AMD was between 0. 011-11. 4 μg·mL-1( r =0.9990) ; LOQ...