Background: Nowadays, there is a need to investigate the potential impact of oxidative stress (OS), particularly as it relates to drug response, to ensure it is warranted and applied in veterinary medicine.
Objectives: We aimed to evaluate the effect of hydrogen peroxide-induced OS on the pharmacological efficacy of nimesulide (NIM) in chickens.
Methods: We assessed the NIM median effective dose (ED50) using the up-and-down method, measured cyclooxygenase 2 (COX2) activity via ELISA, and performed spectrophotometric analysis of NIM concentrations and its pharmacokinetics.
Results: Stressed chickens showed a significant (P<0.05) reduction in total antioxidant capacity (T-AOC) at the 7th, 10th, and 14th days of hydrogen peroxide treatment by 46, 58, and 22%, compared with the control group (tap water). The NIM antinociceptive efficacy increased due to a 31% reduction in ED50 in the stressed chickens. Consequently, there was a significant (P<0.05) inhibition in COX2 activity in both stressed and control chickens by 24 and 30%, respectively. The data also showed a significant (P<0.05) modification in NIM plasma concentration in the stressed chickens compared with the control group at different measurement times. Regarding the NIM pharmacokinetic parameters, OS caused an elevation of the AUC 0-∞, AUMC 0-∞, Cmax, MRT, t1/2β, and Vss by 11, 42, 11, 35, 46, and 39%, respectively, whereas Kel and Cl were decreased by 45 and 8%, respectively.
Conclusion: These results showed that OS modifies the pharmacodynamics and pharmacokinetics of NIM, thereby modifying its pharmacological efficacy; thus, care and adjustment of the NIM dosage are warranted for its use in stressed animals.