Pharmacodynamics and pharmacokinetics interaction between nefopam and tramadol in the broiler chicks model

Abstract

No former studies are dealing with the pharmacological (pharmacodynamics and pharmacokinetics) interaction between nefopam and tramadol in the chicks' model. The median effective doses (ED50s) for nefopam and tramadol produces analgesia has been estimated each alone as 9.24 and 0.83 mg/kg, IP, respectively. The interaction concerning nefopam and tramadol combination was estimated by isobolographic analysis to be 2.91 and 0.25 mg/kg, IP. The kind of interaction between nefopam and tramadol was synergistic as indicated by the interaction index 0.61. The analgesic efficacy of the combination was significantly different from nefopam and tramadol administered alone. Nefopam plasma concentration 18.48 mg/kg, IP for different measured times 0.5, 1, 2, 4, and 24 hours 33.25, 27.10, 15.05, 13.61, and 2.45 µg/ml while the concentration was increased once coadministered with tramadol 1.66 mg/kg, IP by 22, 26, 43, 45, and 81% been 40.72, 34.27, 21.53, 19.76, and 4.43 µg/ml, respectively. Nefopam pharmacokinetic profile comprised of area-under-curve (AUC), area-under-moment-curve (AUMC), mean-residence-time (MRT), half-life (t1/2β), maximal concentration (Cmax) amplified after tramadol is coadministered with nefopam by 52, 260, 23, 15, and 22%. The elimination constant (Kel), distribution volume (VD), clearance (Cl) were diminished 13, 25, and 29%, similarly. The sum results suggested a synergistic interaction between nefopam and tramadol along with a modification in nefopam pharmacokinetic parameters which improve the therapeutic efficacy of nefopam in the chickens besides, advocate using these two drugs as preanesthetics in veterinary medicine.