Kelers K, Devi J L, Anderson G A, Zahra P, Vine J H, Whittem T
Veterinary Hospital, Faculty of Veterinary Science, The University of Melbourne, 250 Princes Highway, Werribee, Victoria, 3030, Australia.
Aust Vet J. 2013 Aug;91(8):312-9. doi: 10.1111/avj.12080.
To compare the bioequivalence and 'switchability' of two formulations of benazepril (tablet and liquid) after oral administration.
Randomised cross-over design, followed by parallel comparison.
Twelve mixed-breed dogs were administered either a tablet (Group A) or liquid formulation (Group B) of benazepril orally at 0.45 mg/kg daily for 4 days. With no washout period, the dogs then received the alternative treatment at the same dose for a further 4 days. Blood samples taken prior to treatment and serially after treatment were analysed for plasma concentrations of benazepril and benazeprilat and the activity and concentration of angiotensin-converting enzyme (ACE). The calculated percentage inhibition of ACE was defined as the primary outcome variable.
No statistically significant differences were found between groups A and B for any variable evaluated. The mean (± SD) percentage of ACE inhibition was 85.5 ± 7.04% for the liquid formulation and 85.9 ± 6.66% for the tablet formulation. The mean of the ratios was 1.00 (80% confidence interval 0.96-1.04). No evaluated effect term (sequence, formulation or period) had any statistical effect on any outcome variable.
This study supports a conclusion that, based on pharmacodynamic response, the liquid formulation of benazepril is bioequivalent to the reference tablet formulation. Further, the lack of a sequence effect supports the switchability of these two formulations.
比较口服两种苯那普利制剂（片剂和液体制剂）后的生物等效性和“可转换性”。
随机交叉设计，随后进行平行比较。
12只杂种犬，每日口服苯那普利片剂（A组）或液体制剂（B组），剂量为0.45mg/kg，共4天。在无洗脱期的情况下，犬只随后以相同剂量接受另一种治疗，持续4天。在治疗前和治疗后连续采集血样，分析苯那普利和贝那普利拉的血浆浓度以及血管紧张素转换酶（ACE）的活性和浓度。计算得出的ACE抑制百分比被定义为主要结局变量。
在评估的任何变量上，A组和B组之间均未发现统计学上的显著差异。液体制剂的ACE抑制平均（±标准差）百分比为85.5±7.04%，片剂制剂为85.9±6.66%。比值的平均值为1.00（80%置信区间0.96 - 1.04）。没有评估的效应项（顺序、制剂或时期）对任何结局变量有任何统计学影响。
本研究支持以下结论，即基于药效学反应，苯那普利液体制剂与参比片剂制剂生物等效。此外，缺乏顺序效应支持这两种制剂的可转换性。
