Influence of hydrogen peroxide in drinking water on diazepam pharmacokinetics in chicks

Aim: Stressful conditions affect drug pharmacokinetics and pharmacodynamics. This study examines the effect of hydrogen peroxide (H O ) in drinking water on the pharmacokinetics of diazepam in a chick model of oxidative stress. 2 2 Materials and Methods: Day old chicks were either provided with plane tap water (control group) or H O in tap water as 2 2 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 H O -treated chicks at mean 2 2 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 H O -treated chicks were significantly higher than those of the control group 2 2 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 H O 2 2 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 H O -treated chicks were 2 2 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 H O -treated chicks decreased from those of the 2 2 respective control values by 15, 24 and 33%. Conclusion: The data suggest that oral exposure of chicks to H O influences the pharmacokinetics of diazepam by 2 2 decreasing its elimination from the body.