Preliminary Investigation of Beagle Dog as Substitute for Humans in Bioequivalence Studies
Purpose: To assess the suitability of beagle dog as an animal model for the evaluation of formulations in bioavailability and bioequivalence studies.
Methods: A generic cetirizine 10 mg tablet formulation was compared with another reference formulation using beagle dog as animal model. A crossover oral comparative bioavailability study was conducted on cetirizine tablet 10 mg in healthy, male dogs under fasting conditions. The formulations were administered orally with the aid of water. Serial blood samples were collected from pre-dose to 48.0 h post-dose and plasma concentrations of cetirizine were determined using validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) analytical method. Pharmacokinetic parameters were calculated using non-compartmental analysis while bioavailability was assessed using an analysis of variance (ANOVA) model for humans and dogs.
Results: Cetirizine plasma concentrations in dog were comparatively higher, in relation to human plasma concentrations, due to the smaller blood volume in former. There was a delay in time to reach maximum plasma concentration (Tmax) in dog. Cetirizine formulations were found to be bioequivalent in either of the species (dog and human). The ratio (test\reference) of least-squares mean for area under plasma concentration curve from time zero to last detectable concentration (AUC0-t), area under plasma concentration curve extrapolated to infinity (AUC0-‡ ) and maximum plasma concentration (Cmax), calculated for the dogs were comparable to those for humans. AUC0-t, AUC0-‡ and Cmax ratios ranged within 92.81 - 106.80 % for dogs and 95.43 . 104.84 % for humans
Conclusion: The results suggest that beagle dogs can be used in place of humans in bioequivalence tests on generic products of cetirizine.
Keywords: Cetirizine, Beagle dog, Bioavailability, Bioequivalence, Pharmacokinetics, Noncompartmental
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