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Original Research
3.
Influence of hydrogen peroxide in drinking water on
diazepam pharmacokinetics in chicks -
Yaareb J. Mousa, Fouad K. Mohammad
Vet World. 2012; 5(11): 658-662
doi:
10.5455/vetworld.2012.
658-662
Abstract
Aim:
Stressful conditions affect drug pharmacokinetics
and pharmacodynamics. This study examines the effect
of hydrogen peroxide (H2O2) in drinking water on the
pharmacokinetics of diazepam in a chick model of
oxidative stress.
Materials and Methods: Day
old chicks were either provided with plane tap water
(control group) or H2O2 in tap water as 0.5% v/v
drinking solution for two weeks in order to produce
oxidative stress. On treatment days 7–14, the chicks
were treated with a sedative dose of diazepam at 10
mg/kg, intramuscularly. Blood samples were obtained
from chicks (5/each sampling time) at times of
between 0.17 to 4 h. The concentrations of diazepam
in the plasma were determined by an HPLC method with
UV-detector. Pharmacokinetic parameters of diazepam
were calculated from the mean drug concentrations in
the plasma by a non-compartmental analysis using a
Windows-based computer program.
Results:
Injection of diazepam resulted in the appearance of
the drug in the plasma of control and H2O2-treated
chicks at mean concentrations ranging between 0.11
to 0.444 and 0.131 to 0.535 μg/ml, respectively when
measured between 0.17 to 4 h after administration.
Diazepam concentrations of the H2O2-treated chicks
were significantly higher than those of the control
group at the sampling times 0.5, 0.75, 1 and 4 h.
The highest concentration of diazepam in the plasma
of both the control and H2O2-treated chicks occurred
one h after the injection. The elimination
half-life, mean residence time, maximum plasma
concentration, area under the moment curve and area
under plasma concentration-time curve in the
H2O2-treated chicks were higher than those of the
control group by 35, 28, 23, 91 and 49%,
respectively. Correspondingly, the steady state
volume of distribution, elimination rate constant
and total body clearance in the H2O2-treated chicks
decreased from those of the respective control
values by 15, 24 and 33%.
Conclusion: The
data suggest that oral exposure of chicks to H2O2
influences the pharmacokinetics of diazepam by
decreasing its elimination from the body.
Keywords: chick, diazepam, half-life, H2O2,
oxidative stress, pharmacokinetics
