Abstract
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.
Highlights
Nefopam belongs to non-narcotic analgesic drugs that cast-off for treatment of modest to severe pain sensation [14] and to manage a neuropathic pain disorder [5]
The objective was to examine the effect of ketorolac on nefopam plasma concentration and its pharmacokinetic parameters besides their possible pharmacodynamics interaction in the chicks as illustrated by isobolographic analysis
As found in this study, the values of ED50s for nefopam and ketorolac combination were decreased in comparison for their values alone suggesting an increase in the analgesic efficacy which is required to produce analgesia in half of the population used as the experimental model
Summary
Nefopam belongs to non-narcotic analgesic drugs that cast-off for treatment of modest to severe pain sensation [14] and to manage a neuropathic pain disorder [5]. Ketorolac aids as peripheral analgesic medication that achieving modest and intense nociception with minimal untoward influences which account a well permitted, operative injectable remedy, inexpensive and economic analgesics medication dissimilar to the central opioids agonists like morphine and tramadol that have serious side effect corresponding to respiratory depression and medical addiction [16,17,18,19,20]. Ketorolac's action taking-place at non-narcotic receptors which lessens the threat of possibly enhancer untoward effects similar to hemo-dynamic modifications, centrally changes in nervous tissue, and respiratory suppression [19]. Ketorolac's properties esteem appropriate medication working along with, cure and management of nociception induced after surgery because of, the pain and inflammation that produced by means of the operations and it provides both analgesic and antiinflammatory effects, in contrast to opioids, that do not provide anti-inflammatory action in this situation and having a slight therapeutic safety [21,22,23]
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