国产和进口雷米普利片的药动学和生物等效性

Pharmacokinetics and bioequivalence of domestic and imported ramipril tablets

目的研究单剂量口服国产和进口雷米普利片在健康受试者体内的药动学特征,评价其是否具有生物等效性。方法采用随机、双交叉试验设计,24名健康男性受试者分别单次口服雷米普利片10 mg(2片)后血浆中雷米普利和雷米普利拉的浓度采用LC-MS/MS法测定,药动学参数用3P97程序进行计算。结果国产与进口制剂中雷米普利的ρmax分别为:(28.26±12.54)(、28.71±12.84)μg.L-1;tmax分别为:(0.61±0.54)、(0.51±0.10)h;AUC0→t分别为:(24.52±13.21)(、22.94±10.93)μg.h.L-1,其主要代谢产物雷米普利拉的ρmax分别为:(24.37±13.65)、(23.65±11.51)μg.L-1;tmax分别为:(2.21±0.81)(、1.96±0.67)h;AUC0→t分别为:(127.21±63.04)(、118.72±56.50)μg.h.L-1。国产及进口制剂的ρmax、AUC0→t、AUC0→∞等药动学参数经对数转换后的统计学处理(方差分析及双单侧t检验),国产与进口制剂药物间差异均无统计学意义(P>0.05)。国产制剂的相对生物利用度雷米普利为(105.42±22.23)%,雷米普利拉为(107.29±20.40)%(n=24)。结论国产与进口雷米普利片具有生物等效性。

AIM To study the pharmacokinetics and bioequivalence of domestic and imported ramipril tablets in healthy subjects. METHODS Twenty-four healthy male subjects in a randomized crossover design were given a single oral dose of 10 mg ramipril. Plasma concentrations of the subjects were determined by LC-MS/MS. The pharmacokinetic parameters were calculated from 3P97 software. RESULTS The main pharmacokinetic parameters of domestic and imported formulations of ramipril were as follows： ramipril： ρmax were （28.26 ± 12.54）, （28.71 ±12.84）μg.L^-1; tmax were （0.61 ± 0.54）, （0.51 ± 0.10） h; AUC0→t were （ 24.52 ± 13.21 ）, （ 22.94 ± 10.93） μg. h.L^-1. The main metabolite-ramiprilat： ρmax were （24.37 ± 13.65）, （23.65 ± 11.51 ） μg.L^-1 ; tmax were （ 2.21 ± 0.81 ）, （ 1.96 ±0.67） h ; AUC0→t were （ 127.21 ± 63.04）, （ 118.72 ± 56.50） μg.h.L^-1, respectively, The statistic analysis of the two formulations were calculated by analysis of variance, two one-sided t tests and confidence intervals. The results of rarnipril and ramiprilat demonstrated that there were no significant differences between domestic and imported formulations （P 〉 0.05）. The mean relative bioavailability of domestic formulation of ramipril was （ 105.42 ± 22.23） %, ramiprilat was （107.29±20.40） %（n =24）. CONCLUSION The domestic and imported mmipril are bioequivalent.