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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 study the pharmacokinetics of doxorubicin in Beagle dogs treated with chlorogenic acid and doxorubicin. Methods Beagle dogs were randomly divided into doxorubicin group and combination group. Blood samples were collected after intravenous administration, serum was prepared and plasma concentration was determined by HPLC. The chromatographic column was Aichrombond-AQC18 (150 mm × 4.6 mm, 5 μm) with a mobile phase of 0.01 mol·L -1 KH 2 PO 4 -methanol-acetonitrile-formic acid (50:40:10:0.1) at a flow rate of 1.0 mL · min -1 . Results The linear relationship between the concentration of doxorubicin and the peak area was 0.011 ~ 11.4μg · mL-1 (r = 0.9990). The minimum detectable concentration was 5.25ng · mL-1. Adriamycin before and after combination therapy showed two-compartment model; Cmax was 0.457,0.557mg · L-1, Tmax was 15,15min, T1 / 2 was 18.70,22.79min, Cl was 0.029,0.027L · min-1 · kg -1, AUC was 54.99, 59.53 mg · L-1 · min-1, relative bioavailability was 115.40%. Conclusions Chlorogenic acid has no significant effect on doxorubicin pharmacokinetic model after combined treatment. However, the clearance rate of doxorubicin slightly decreased, the half-life and AUC increased, and the bioavailability significantly increased (P <0.05). Chlorogenic acid and doxorubicin combination therapy, can increase the treatment of doxorubicin concentration, and a slight increase in half-life.