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目的研究阿霉素和绿原酸联合用药前后在大鼠体内药物代谢动力学的规律。方法将SD大鼠随机分成阿霉素、绿原酸和联合给药组。HPLC-UV法分别测定各试验组在不同时间点大鼠血清中的药物浓度,计算药动学参数,并模拟出各自的动力学模型。结果阿霉素0.011~10.500μg.ml-1(r=0.9993)、绿原酸0.252~1260.000μg.ml-1(r=0.9998)与峰面积有良好的线性关系;最低定量浓度分别为0.011、0.252μg.ml-1;联合用药后,阿霉素和绿原酸的体内动力学模型均无明显变化,半衰期分别为105.4、48.4 min,清除率为0.011、0.001 L.min-.1kg-1,AUC为167.7、6743 mg.L-.1min,生物利用度为161.7%、109.5%。结论阿霉素与绿原酸联合用药对大鼠的体内动力学模型无明显影响,但阿霉素的清除率和AUC有显著性差异,生物利用度有显著性提高(P<0.05);联合用药时,可适当降低阿霉素的剂量,以增加临床治疗的安全性。
Objective To study the pharmacokinetics of adriamycin and chlorogenic acid in rats before and after administration. Methods SD rats were randomly divided into adriamycin, chlorogenic acid and combination group. HPLC-UV method was used to determine the concentration of drug in rat serum at different time points. The pharmacokinetic parameters were calculated and their kinetic models were simulated. The results showed that there was a good linear relationship between the doxorubicin concentration and peak area of 0.011 ~ 10.500μg.ml-1 (r = 0.9993), chlorogenic acid 0.252 ~ 1260.000μg.ml-1 (r = 0.9998) 0.252μg.ml-1; After combined treatment, the in vivo kinetic models of doxorubicin and chlorogenic acid had no significant change, the half-lives were 105.4,48.4 min, the clearance rates were 0.011,0.001 L.min-1kg-1 , AUC was 167.7,6743 mg.L-1min, bioavailability was 161.7%, 109.5%. Conclusion The combination of doxorubicin and chlorogenic acid has no significant effect on the in vivo kinetic model of rats. However, the clearance rate of adriamycin and AUC are significantly different, and the bioavailability is significantly increased (P <0.05) Medication, may be appropriate to reduce the dose of doxorubicin to increase the safety of clinical treatment.