多潘立酮咀嚼片的人体药动学和生物等效性

Pharmacokinetics and Bioequivalence of Domperidone Chewable Tablets in Healthy Volunteers

目的研究多潘立酮咀嚼片和普通片在中国健康人体中的药动学及生物等效性。方法18名健康男性受试者单次口服10 mg多潘立酮咀嚼片和多潘立酮普通片后,采用LC-MS/MS测定多潘立酮的血药浓度,并计算两制剂的主要药动学参数及相对生物利用度。结果多潘立酮咀嚼片和普通片的主要药动学参数tmax分别为(0.59±0.29)和(0.67±0.43)h,ρmax分别为(11.27±4.31)和(10.87±4.31)μg.L-1,t1/2分别为(6.97±1.96)和(6.97±2.34)h,AUC0-t分别为(37.89±13.15)和(37.54±12.53)μg.h.L-1,AUC0～∞分别为(41.53±13.96)和(41.67±13.56)μg.h.L-1;两制剂的药动学参数基本相同,咀嚼片的相对生物利用度为(102.35±21.85)%。ρmax,AUC0-t,AUC0-∞采用双向单侧t检验,并经对数转换后,进行统计学方差分析,tmax采用Wilcoxon符号秩和检验,显示两制剂间无显著性差异(P>0.05)。结论多潘立酮咀嚼片和普通片在人体内处置过程基本一致,2种制剂具生物等效,临床上可以替换使用。

OBJECTIVE To study pharmacokinetics and bioequivalence of dompefidone chewable tablets in healthy Chinese volunteers. METHODS A single oral dose of 10 mg tested domperidone chewable tablets or reference domperidone tablets was given to 18 healthy volunteers in a randomized crossover study. The plasma sample was deproteined by precipitation with methanol and determined by LC-MS/MS method. The pharmacokinetic and relative bioavailability were studied. RESULTS The pharmacokinetic parameters of test and reference formulations were as follows： tmax （0.59±0.29） and （0.67±0.43） h, ρmax（11.27±4.31） and （10.87±4.31）μg·L^-1, t1/2（6.97±1.96） and （6.97±2.34） h, AUC0-t （37.89±13.15） and （37.54±12.53）μg·h·L^-1, AUC0-∞ （41.53±13.96） and （41.67±13.56）μg·h·L^-1. The relative bioavailability of test to reference tablets was （102.35±21.85）%. ρmax, AUC0-t and AUC0-t were tested by two one-side test and analyzed for bioequivalenee after log transformation of data. tmax was analyzed by Wilcoxon＇s test. No significant difference was found between two preparations （P〉0.05） . CONCLUSION The results demonstrated that the two preparations were found to be bioequivalent and thus, can be prescribed interchangeably.