Iraqi Journal of Veterinary Sciences, Vol. 36, No. 2, 2022 (327-332) 327 Iraqi Journal of Veterinary Sciences www.vetmedmosul.com Pharmacodynamics and pharmacokinetics interaction between nefopam and tramadol in the broiler chicks model Y.J. Mousa 1 and M.B. Mahmood 2 1 Department of Physiology, Biochemistry and Pharmacology, College of Veterinary Medicine, University of Mosul, Mosul, 2 Department of Internal Medicine, Surgery and Pharmacology, College of Veterinary Medicine, University of Dohuk, Dohuk, Iraq Article information Abstract Article history: Received May 23, 2021 Accepted July 11, 2021 Available online February 2, 2022 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. Keywords: Chicks Nefopam Pharmacodynamics Pharmacokinetics Tramadol Correspondence: Y.J. Mousa yarub204@uomosul.edu.iq DOI: 10.33899/ijvs.2021.130163.1746, ©Authors, 2022, College of Veterinary Medicine, University of Mosul. This is an open access article under the CC BY 4.0 license (http://creativecommons.org/licenses/by/4.0/). Introduction Nefopam belongs to non-narcotic medications generally of benefit for the management of mild to serious acute or chronic discrimination or used for treating neuropathic ache disorders (1) and acetaminophen coadministration could potentiate its analgesic effect (2). Nefopam can lead to stronger, deeper, and more durable illnesses without causing respiratory depression similar to morphine through its central acting on the brain and spinal cord (3-5). Nefopam acts through a specific mechanism for action by either altering the Na +2 and Ca +2 channels via decreasing glutamate neurotransmitter release (which is considered to be a key pain-related neurotransmitter) or by increasing catecholamines (especially norepinephrine and dopamine) and serotonin by their rehabilitation of the presynaptic neurons (6). Tramadol is an opioid drug that is commonly used for developing its antinociceptive properties in animals and humans through its mode of action against mu receptors on the central nervous system through inhibiting the re-uptake of norepinephrine and serotonin (7-9). Tramadol is considered a good pain relief but produces