Amantadine produces analgesia through a unique mechanism and pharmacokinetics in chickens

Abstract

Nowadays, there is a requisite for worthy and effective analgesic drugs with the least side effects for proper use in veterinary medicine. The goal was to relate amantadine (AMN) pharmacodynamics (i.e. analgesia and COX-2 inhibition) with a preferential (nimesulide) COX-2 inhibitor besides detecting its pharmacokinetics in chickens. Methodology included assessing the analgesic median effective dose (ED50), kidney and liver functions, Brain COX-2 activity, and AMN plasma concentration with its pharmacokinetics profile in the chickens. The analgesic ED50 of AMN was found to be 15.72 mg/kg, orally (P.O.). Oral administration of AMN (31.44 mg/kg) did not significantly alter the liver and kidney functions, as there were no significant changes in the aspartate transaminase (AST) and alanine transaminase (ALT), as well as uric acid and creatinine. AMN (31.44 mg/kg, P.O.) along with nimesulide (20 mg/kg, intramuscularly) significantly inhibit COX-2 activity in the whole brain of chickens associated with the control animals by 26 and 14%, respectively. Plasma concentrations of AMN (31.44 mg/kg, P.O.) assessed at variant comparable times (0.25, 0.5, 1, 2, 4, and 8 hours) were 0.38, 0.42, 0.31, 0.30, 0.26 and 0.23 µg/ml. AMN pharmacokinetic variables were estimated to be AUC0-∞ 7.44, AUMC0-∞ 170.85, kel 0.04, Cmax 0.42, Tmax 0.5, t1/2β 15.88, MRT 3.34, Vss 96.75, and Cl 4.22. The study concluded the safety of AMN (liver and kidney functions besides its pharmacokinetics) with its unique capability to modulate the activity of brain COX-2 which makes it a good analgesic, and probably anti-inflammatory drug to be used in chickens.

Keywords

• amantadine
• cox-2
• nociception
• nmda blockers
• pharmacodynamics