对乙酰氨基酚口服混悬液在Beagle犬体内相对生物利用度研究

The Study on the Relative Bioavailability of Paracetamol Oral Suspension in Beagle Dogs

建立Beagle犬血浆中对乙酰氨基酚的药物浓度测定方法,考察对乙酰氨基酚口服混悬液受试制剂和对乙酰氨基酚口服混悬液(泰诺林)参比制剂的相对生物利用度。采用HPLC-MS/MS测定Beagle犬经口给予对乙酰氨基酚口服混悬液受试制剂和参比制剂(泰诺林)后体内血药浓度,计算两者药动学参数,用SPSS统计软件进行统计分析。结果表明,建立的HPLC-MS/MS检测方法重现性良好且稳定,达到了进行药代动力学试验的要求。对乙酰氨基酚在Beagle犬体内的血药浓度-时间曲线符合二房室模型;受试制剂和参比制剂的平均AUC(0-t)分别为(10564±3157)mg/m L·h^(-1)和(10539±2643)ng/m L·h^(-1);平均C_(max)分别为(10162±1745)ng/m L和(9213±1315)ng/m L;两制剂的C_(max)和AUC_((0-t))经统计,均没有显著性差异(P>0.05),相对生物利用度为100%。以同等给药剂量经口给予Beagle犬受试制剂和参比制剂,二者的生物利用度相同。

Objective:To establish a method for determination of acetaminophen concentration in Beagle dog plasma,and to investigate the relative bioavailability of acetaminophen oral suspension preparation and acetaminophen oral suspension(Tylenol)reference preparation..Methods:HPLC-MS/MS was used to determine the in vivo blood concentration of Beagle dogs after oral administration of acetaminophen oral suspension and reference preparation(Tylenol).The pharmacokinetic parameters of the two were calculated and statistically analyzed with SPSS statistical software.Results:The established HPLC-MS/MS method had good reproducibility and stability,and met the requirements of pharmacokinetic test.The results showed that the concentration-time curve of acetaminophen in beagle dogs was in accordance with the two compartment model.The main pharmacokinetic parameters AUC(0-t)were 10564±3157 ng/(m L·h)and 10539±2643 ng/(m L·h),C_(max)were 10162±1745 ng/m L and 9213±1315 ng/m L.The C_(max)and AUC(0-t)of the two preparations showed no significant difference(p>0.05),and the relative bioavailability was 100%.Conclusion:The bioavailability of test preparation and reference preparation in beagle dogs is the same when given orally with the same dose.