Effects of hydrogen peroxide-induced oxidative stress on the plasma concentration and pharmacokinetics of ketorolac in chicks

Abstract

The aim was to determine the impact of oxidative stress (OS), induced by hydrogen peroxide (H2O2), on the ketorolac plasma concentration and pharmacokinetics in the chicks. A significant decrease was observed in the total antioxidant status (TAS) measured on day 7th, 10th, and 14th of chicks age by 39, 29, and 41%, respectively compared to the control (H2O) group. By measuring the analgesic median effective dose (ED50), ketorolac’s analgesia amplified 16% in the stressed (H2O2) group. Ketorolac concentration in plasma was investigated at measured multiple times at 0.25, 0.5, 1, 2, 4, and 24 hours after the administration (14 mg/kg, IM) to 110.38, 181.46, 66.24, 13.08, 10.11, and 4.12 µg/ml at the H2O group and significantly elevated in all times measured except 0.25 and 24 h after ketorolac administration by 24, 38, 54, 199, 93, and 59 % to be 136.45, 250.88, 102.03, 39.13, 19.55, and 6.55 µg/ml in the H2O2 group, respectively. The values of AUC0-∞, AUMC0-∞, Cmax, and Kel in the stressed chickens that were administered ketorolac were elevated by 59, 19, 38, and 43%, respectively, whereas other parameters like MRT, t1/2β, Vss, and Cl were reduced by 25, 30, 56, and 37% respectively compared to H2O group. The results showed that the H2O2-inducedOS amplified the analgesic action of ketorolac in a chick model, besides its modification of the plasma concentration and pharmacokinetics of ketorolac.