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Bioequivalence of a new liquid formulation of benazepril compared with the reference tablet product
K Kelers1, J L Devi, G A Anderson
1Veterinary Hospital, Faculty of Veterinary Science, The University of Melbourne, 250 Princes Highway, Werribee, Victoria, 3030, Australia. kkelers@unimelb.edu.au
Objective:
To compare the bioequivalence and 'switchability' of two formulations of benazepril (tablet and liquid) after oral administration.
Design:
Randomised cross-over design, followed by parallel comparison.
Methods:
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.
Results:
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.
Conclusion:
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.
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