阿莫西林混悬注射液在猪体内的生物等效性研究

Study on Pharmacokinetics of amoxicillin suspension injection in pigs

关键词:  阿莫西林混悬注射液  高效液相色谱法  药动学  生物等效性

Key words:  Bioequivalence of Amoxicillin Suspension Injection in Pigs

摘要:

研究阿莫西林混悬注射液在猪体内的药代动力学及生物等效性。采用双处理、双周期随机交叉试验设计，将24头健康猪随机分成2组，按15 mg/kg体重肌肉分别单剂量注射受试制剂和参比制剂，采用高效液相色谱法测定血浆中阿莫西林的浓度，利用WinNonlin6.4软件计算主要药动学参数，并评价两种制剂的生物等效性。结果显示，受试制剂和参比制剂的Tmax分别为（3.45±2.49）h，（1.34±1.74）h；Cmax分别为（6.94±4.73）mg/L，（4.39±2.87）mg/L；AUC0-t分别为（37.00±11.48）mg?h?L-1，（30.02±8.93）mg?h?L-1；AUC0-∞分别为（40.26±13.36）mg?h?L-1，（38.46±15.38）mg?h?L-1。阿莫西林混悬注射液受试制剂和参比制剂的AUC0-t、AUC0-∞、 Cmax、Tmax均有显著性差异，双单侧t检验结果显示两种制剂生物不等效，试验为兽医临床给药方案的制定以及合理用药提供参考。

Abstract:

To evaluate the pharmacokinetics and bioequivalence of amoxicillin suspension injection in pigs. In a randomized two - way self – crossover study, 24 healthy pigs were randomly divided into two groups, and were given respectively a single dose of test or reference preparations by intramuscular injection(15 mg/kg). Plasma concentrations of amoxicillin were measured by HPLC. The pharmacokinetic parameters were calculated by WinNonlin6.4 software, and the bioequivalence were evaluated. The main pharmacokinetic parameters of the test and reference preparations were as follows: Tmax were（3.45±2.49）h，（1.34±1.74）h；Cmax were（6.94±4.73）mg/L，（4.39±2.87）mg/L；AUC0-t were （37.00±11.48）mg?h?L-1，（30.02±8.93）mg?h?L-1；AUC0-∞ were （40.26±13.36）mg?h?L-1，（38.46±15.38）mg?h?L-1. The pharmacokinetic parameters (AUC0-t、AUC0-∞、Cmax、Tmax) showed significant difference between test and reference preparations of amoxicillin suspension injections. The test and reference formulations are not bioequivalent after two one-side t-test. This study will provide theoretical basis for making of veterinary clinical dosage regimen and clinical rational administration.