盐酸贝那普利咀嚼片在犬体内的生物等效性研究

Study on Bioequivalence of Benazeptil hydrochloride Tablets in Dogs

关键词:  盐酸贝那普利  贝那普利拉  生物等效性  超高效液相色谱串联质谱

Key words:  benazeptil hydrochloride  benazeprilate  bioequivalence  UPLC-MS/MS

摘要:

为研究国产和进口盐酸贝那普利片在犬体内的药代动力学和生物等效性，将20只健康比格犬随机分成2组，采用双周期交叉试验设计，按0.5 mg/kg体重分别单剂量口服受试产品和参比产品。采用UPLC-MS/MS法测定血浆中盐酸贝那普利及贝那普利拉的浓度，利用WinNonlin5.2.1软件计算主要药动学参数，并评价两种产品的生物等效性。结果显示，受试产品和参比产品中盐酸贝那普利Tmax分别为（0.85±0.36）h和（0.98±0.40）h；Cmax分别为（65.85±31.14）ng?mL-1和（52.02±25.79）ng?mL-1；AUC0-t分别为（46.98±29.77）h?ng?mL-1和（40.54±20.76）h?ng?mL-1；AUC0-∞分别为（48.28±30.05）h?ng?mL-1和（41.54±20.85）h?ng?mL-1；受试产品和参比产品的贝那普利拉Tmax分别为（1.78±0.55）h和（1.90±0.72）h；Cmax分别为（63.05±28.44）ng?mL-1和（55.29±36.01）ng?mL-1；AUC0-t分别为（249.09±87.90）h?ng?mL-1和（212.50±90.03）h?ng?mL-1；AUC0-∞分别为（274.15±93.86）h?ng?mL-1和（264.42±161.86）h?ng?mL-1。受试产品和参比产品的Tmax、Cmax、AUC0-t和AUC0-∞均无显著性差异（P>0.05）。双单侧t检验及90%置信区间结果均提示两种制剂生物等效，临床上可相互替代。该试验为兽医临床安全使用该药提供科学的依据。

Abstract:

To study the pharmacokinetics and bioequivalence of domestic and imported benazepril hydrochloride in dogs, 20 healthy Beagle dogs were randomly divided into two groups. A two-period crossover trial was designed to batches the tested product and reference product at a single dose of 0.5 mg / kg body weight, respectively. The plasma concentrations of benazepril and benazeprilat was analysed by UPLC-MS/MS. The pharmacokinetic parameters were calculated by WinNonlin5.2.1 software and the bioequivalence of the two products was evaluated. The results showed that the Tmax of benazepril hydrochloride in the tested and reference products were (0.85 ± 0.36) h and (0.98 ± 0.40) h，respectively, Cmax were（65.85±31.14）ng?mL-1 and （52.02±25.79）ng?mL-1；AUC0-t were（46.98±29.77）h?ng?mL-1 and（40.54±20.76）h?ng?mL-1；AUC0-∞were（48.28±30.05）h?ng?mL-1 and （41.54±20.85）h?ng?mL-1. The Tmax of Benazeprila and the reference product were (1.78 ± 0.55) h and (1.90 ± 0.72) h, respectively, Cmax were（63.05±28.44）ng?mL-1 and （55.29±36.01）ng?mL-1；AUC0-t were（249.09±87.90）h?ng?mL-1 and （212.50±90.03）h?ng?mL-1；AUC0-∞were（274.15±93.86）h?ng?mL-1 and （264.42±161.86）h?ng?mL-1. There was no significant difference in Tmax, Cmax, AUC0-t and AUC0-∞ between the two formulations (P>0.05). Double unilateral two one-side t-test and 90% confidence interval results suggest that the two formulations are bioequivalent and clinically interchangeable. The trial provides a scientific basis for veterinary clinical use of the drug.