卡维地洛自乳化分散片在大鼠体内的药动学研究

Pharmacokinetic study of Carvedilol Self-emulsifying Dispersible Tablets in rats

目的建立卡维地洛自乳化(CAR SEDDS)分散片在大鼠体内的血药质量浓度测定方法,并对其体内药动学行为进行研究。方法建立HPLC法测定血样中卡维地洛(CAR)的质量浓度。流动相为甲醇-0.033 mol·L^(-1)磷酸盐缓冲液(PBS)-冰醋酸(60∶40∶0.3);流速为1 mL·min^(-1);检测波长为242 nm。大鼠分别灌胃给予CAR SEDDS分散片和市售制剂,并在给药后多点眼眶采血,测定血浆中CAR的质量浓度,采用PK Solver软件计算药动学参数。结果 CAR的线性范围为0.03~5.00μg·mL^(-1),日内和日间精密度的RSD值均小于5.00%,低、中和高质量浓度方法的回收率均符合要求。与市售制剂相比,CAR SEDDS分散片的C_(max)显著提高,相对生物利用度为230.45%。结论建立的检测方法准确,可用于CAR SEDDS分散片血药质量浓度的测定。与市售制剂相比,CAR SEDDS分散片可显著提高CAR的生物利用度。

Objective To establish the plasma concentration measurement method and to study the pharmacokinetic profiles of Carvedilol Self-emulsifying(CAR SEDDS)Dispersible Tablets in rats.Methods An HPLC method was developed to determine the content of carvedilol in the blood samples from rats.The mobile phase consisted of methanol-0.033 mol·L-1 phosphate buffer solution(PBS)-acetic acid(60∶40∶0.3).The flow rate of mobile phase was 1 mL·min-1.The wavelength of UV detection was 242 nm.Rats were given CAR SEDDS Dispersible Tablets and commercial capsules,and the blood from the eye vein was collected at different time after administration.According to the results of the concentration of carvedilol in plasma,parameters were calculated with PK Solver software.Results The linear range was 0.03-5.00μg·mL-1.The RSD of within-day and between-days was below 5.00%.The recoveries of the methods with low,middle and high concentrations all met the requirements.Compared with commercial preparation,C max of CAR SEDDS Dispersible Tablets was significantly improved and the relative bioavailability was 230.45%.Conclusion The method was accurate and reliable,which can be used to determine carvedilol in plasma and study the pharmacokinetic profiles.Compared with commercial preparation,CAR SEDDS Dispersible Tablets could significantly improve the oral bioavailability of the drug.