BIOAVAILABILITY AND DISPOSITION KINETICS OF AMOXICILLIN

IN NORMAL AND WATER DEPRIVED (DEHYDRATED) RABBITS

Abstract

OBJECTIVE: The study was planned to observe the bioavailability and
disposition kinetics of amoxicillin in adult rabbits (irrespective of sex) under healthy and
dehydrated conditions. Design: Comparative. Place and duration of study: The study was
conducted at the department of pharmacology, University of Veterinary and Animal Sciences,
Lahore from April 2013 to October 2013. Methodology: Initially all rabbits were weighed and
their packed cell volume (PCV) and other biochemical parameters were observed under normal
conditions. Bioavailability and disposition kinetics of amoxicillin (10mg/kg body weight) were
studied in normal rabbits following oral and intravenous route of drug administration. After 10
days washout period, these rabbits were made dehydrated by keeping the animals off water
but not food. The animals with 10% decrease in body weight were declared dehydrated. Their
parameters were again measured. Treated rabbits were administered amoxicillin orally and
intravenously (10mg/kg body weight). Samples were drawn at prescribed time. Amoxicillin
was assessed in plasma by using microbiological assay method. Plasma concentration was
analyzed using non compartmental method. Results: The water deprived or dehydrated rabbits
showed a significant increase in the packed cell volume, blood glucose and plasma globulins as
compared to the normal rabbits. However, there was a significant (p<0.05 & p<0.01) decrease
in body weight, total proteins, albumins and albumin globulin ratio of the dehydrated rabbits.
The peak plasma concentration, volume of distribution and rate constant of elimination was
lower in the dehydrated rabbits as compared to the normal rabbits. The plasma concentration
of amoxicillin after intravenous administration in dehydrated rabbits had a significant (p<0.05
& p<0.01) larger area under curve, area under 1st moment curve, a longer half life and a larger
mean residence time. Conclusions: The study in the dehydrated rabbits indicated the need of
modification of dosage regimen.