阿霉素与绿原酸在大鼠体内药动学的相互作用

Pharmacokinetics interactive effects between Adriamycin and chlorogenic acid in rats

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—10．500ug·ml^-1（r=0．9993）、绿原酸0．252—1260．000ug·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、0．252ug·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、48．4min，清除率为0．011、0．001L·min^-1·kg^-1，AUC为167．7、6743mg·L^-1·min，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 investigate the interactive effects between Adriamycin and chlorogenic acid（CA） in rats by studying the pharmacokinetics changes before and after drug combination administration. METHODS The rats were divided into ADM, CA and drug combination groups randomly. The drug plasma concentrations in rats by HPLC - UV in different groups and different time points were determined. The pharmakinetics parameters and pharmakinetics model were calculated by DAS soft. RESULTS Both ADM and CA had good linearities between 0.011 - 10. 500 ug·ml^-1 （ r = 0. 9993 ） and 0. 252 - 1260. 000 ug·ml^-1 （ r = 0. 9998 ） , respectively; The LOQ were 0.011ug·ml^-1 and 0.252ug·ml^-1, respectively. There was no change of the models after drug combination administration. T1/2γ, Cl ,AUC and bioavailability of these two drugs were 105.4, 48.4 min; 0.011, 0. 001 L·min^-1·kg^-1; 167.7,6743 mg·L^-1. min and 161.7% , 109.5% , respectively. CONCLUSION There are no obvious changes in rats pharmacokinetics models after drug combination of AMD and CA. But T1/2 , Cl and AUC have changed greatly;the bioavailability of ADM has increased significantly （ P 〈 0.05 ） ; It is inferred that CA can reduce the toxicity of ADM and enhance its safety by drug combination.