Nefopam and ketorolac: Isobolographic analysis of analgesic effect and pharmacokinetic profile in chicks

Abstract EN

There are no prior studies on the pharmacological interaction between nefopam and ketorolac and on their pharmacokinetics in the chickens.

the median analgesic effective doses (ED50s) of nefopam and ketorolac were estimated individually as 8.39 mg / kg, i.m.

for each drug.

thereafter, their values were determined together in combination as 2.63 and 2.63 mg / kg, i.m.

after administration at the ratio of 1:1 of their ED50s.

the pharmacodynamic interaction between nefopam and ketorolac was designated as synergistic through the interaction index 0.62.

plasma concentrations of nefopam alone 16 mg / kg, i.m.

in different measured times 0.25, 0.5, 1, 2, 4, and 24 hours were 34.07, 31.34, 22.53, 19.03, 14.81, and 10.37 μg / ml, whereas the plasma concentrations increased to become 44.67, 43.52, 45.71, 32.83, 20.96, and 22.54 μg / ml when administered with ketorolac 16 mg / kg, i.m.

by 31, 39, 103, 73, 42, and 117 %, respectively.

the changes in the pharmacokinetic parameters of nefopam included increases in area under curve (auc0-∞) 130%, area under moment curve (AUMC0-∞) 210%, mean residence time (MRT) 35%, half-life (t1 / 2β) 27%, time maximum (TMAX) 300% and concentration maximum (CMAX) 34%, whereas other values were reduced which included elimination rate constant (KEL) 21%, volume of distribution at steady state (VSS) 45% and clearance (CL) 3%.

the net results indicated a synergistic interaction between nefopam and ketorolac in addition to an alteration in nefopam pharmacokinetic parameters which may enhance nefopam therapeutic efficacy in chicks.