Influence of Xylazine on the Plasma Concentration and Pharmacokinetics of Nefopam in Chickens

Abstract

There are no prior studies on the pharmacological influence of xylazine on the plasma concentration and pharmacokinetics of nefopam in chickens. The median analgesic effective doses (ED_50s) of nefopam and xylazine were estimated individually as 9.75 and 1.65 mg/kg, i.m., respectively. Thereafter, their values were determined together in combination as 3.17 and 0.55 mg/kg, i.m. after administration at the ratio of 1:1 of their ED_50s. The pharmacodynamic interaction between nefopam and xylazine was designated as synergistic through the interaction index 0.66. The plasma concentration of nefopam alone (19.50 mg/kg, i.m.) estimated through different times (0.25, 0.5, 1, 2, 4, and 24 hours) were 349.83, 652.73, 564.38, 513.90, 406.63 and 349.83 µg/ml whereas the plasma concentration of nefopam and xylazine (19.50 and 3.30 mg/kg, i.m. respectively) was elevated to became 791.55, 1568.98, 854.65, 690.59, 488.66 and 400.31 µg/ml by 126, 140, 51, 34, 20 and 14 %, respectively. The changes in the pharmacokinetic parameters of nefopam included decreases in area under curve (AUC_0-∞)(9%), area under moment curve (AUMC_0-∞)(39%), mean residence time (MRT)(33%), half-life (t_1/2β)(33%) and volume of distribution at steady state (V_ss)(26%), whereas other values were increased which included concentration maximum (C_max) (58%), elimination rate constant (K_el)(32%), and clearance (Cl)(14%). The net results indicated a synergistic interaction between nefopam and xylazine in addition to an alteration in nefopam pharmacokinetic parameters which may enhance nefopam therapeutic efficacy in chicks.