Preliminary Investigation
of Beagle Dog as Substitute for Humans in Bioequivalence
Studies
Hari Krishan Tiwari1*,
Priya Ranjan Prasad Verma2; Tausif
Monif1,
Rachna Arora1
and Simrit Reyar1
1Department of Clinical
Pharmacology and Pharmacokinetics, Ranbaxy Research
Laboratories, Plot GP-5, Sec-18, HSIIDC, Old Delhi-Gurgaon
Road, Gurgaon-122 015, Haryana, 2Birla
Institute of Technology, Ranchi, Jharkhand, India.
*For correspondence:
Email:
hari.tiwari@ranbaxy.com; Tel:
+ 91-124- 4768051; Fax:
+91-124-4231002
Received: 5 December 2013
Revised accepted: 17
January 2014
Tropical Journal of
Pharmaceutical Research, March 2014;
13(3):
383-389
http://dx.doi.org/10.4314/tjpr.v13i3.11
Abstract
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, Non- compartmental.
