Pharmacokinetics of flunixin meglumine （FM） was investigated in 14 healthy pigs following single intravenous （i.v.） and intramuscular （i.m.） administration of the drug at the dosage of 2.2 and 1.1 mg kg-1. Blood...Pharmacokinetics of flunixin meglumine （FM） was investigated in 14 healthy pigs following single intravenous （i.v.） and intramuscular （i.m.） administration of the drug at the dosage of 2.2 and 1.1 mg kg-1. Blood samples were collected at different intervals after administration, and concentrations of FM were determined by HPLC method with a limit of detection of 0.1μg mL-1. The FM concentration-time data were fitted to a two-compartment open model after single i.v. dosing in pigs. The main pharmacokinetic parameters were as follows： tl/2a, 0.49 ± 0.03 and 0.58±0.07 h; tl/2β, 6.28±0.13 and 7.37 ±0.59 h; V/F, 0.01 ±0.001 and 0.01 ±0.002 L kg-1; CL, 0.01 ± 0.002 and 0.01 ± 0.002 L h-l; AUC, 237.73 ± 52.46 and 147.71 ± 36.76μg h-1 mL-1. The drug concentration-time data were fitted to a two-compartment model with first-order absorption after single i.m. administration in pigs. The main pharmacokinetic parameters were as follows： t1/2α, 0.90± 0.07 and 0.86±0.10 h; t1/2β, 8.79±0.85 and 9.60±0.10 h; V/F, 0.02±0.004 and 0.02±0.003 L kg-1; CL, 0.01±0.002 and 0.01 ±0.003 L h-l; AUC, 174.63 ± 45.84 and 112.42 ± 31.19 pg h-1 mL 1. The results of the present study showed that FM was rapidly absorbed, extensively distributed, and slowly eliminated in pigs. The drug was completely absorbed after single i.m. administration and a good bioavailability in pigs.展开更多
氟尼辛葡甲铵盐是一种动物专用的非甾体抗炎药,具有镇痛和解热功能,但抗炎是其主要功效。本试验通过对鸡蛋清诱导的大鼠踝关节炎性肿胀模型和冰醋酸所致小鼠疼痛扭体反应来研究其抗炎镇痛效果。与对照组相比,FM高中低各剂量组(0.55、1.1...氟尼辛葡甲铵盐是一种动物专用的非甾体抗炎药,具有镇痛和解热功能,但抗炎是其主要功效。本试验通过对鸡蛋清诱导的大鼠踝关节炎性肿胀模型和冰醋酸所致小鼠疼痛扭体反应来研究其抗炎镇痛效果。与对照组相比,FM高中低各剂量组(0.55、1.1、2.2 m g/kg)对大鼠足关节炎症均有显著的对抗作用(P<0.05,P<0.01),呈明显的量效关系。高剂量组(2.2m g/kg)抗炎功效明显优于吲哚美辛组(2.25 m g/kg)和地塞米松组(2.52 m g/kg)。中剂量组(1.1 m g/kg)作用堪比吲哚美辛,而低剂量组(0.55 m g/kg)稍逊于地塞米松。与同类对照药双氯芳酸钠(16.25 m g/kg)和安乃近(32.5 m g/kg)相比,结果显示FM(2.5 m g/kg)对小鼠扭体抑制作用最强,抑制率高达82.69%。展开更多
To investigate the effect of Flunixin meglumine- a NSAID;alone and in combination with hypertonic saline on endotoxemic buffalo calves, two groups of five apparently healthy male buffalo calves aged be-tween 6-8 month...To investigate the effect of Flunixin meglumine- a NSAID;alone and in combination with hypertonic saline on endotoxemic buffalo calves, two groups of five apparently healthy male buffalo calves aged be-tween 6-8 months were subjected to I.V. infusion of E.coli endotoxin at the rate of 5μg/kg BW per hour for 3 hours. A highly significant (P < 0.01) fall in mean systolic,diastolic, pulse, mean arterial pressure (M.A.P), central venous pressure (C.V.P) and haemo-globin was observed till the end of endotoxin infusion while respiratory rate was significantly elevated along with a non-significant alteration in rectal tem-perature and hematocrit during the infusion of en-dotoxin. Immediately at the end of endotoxin infusion, flunixin meglumine at the rate of 1.1 mg/kg B.W was infused i.v. in group-I animals and group-II animals were infused with hypertonic saline solution (H.S.S.) at the rate of 4 ml/Kg BW as one time infusion fol-lowed by flunixin meglumine at the rate of 1.1 mg/kg B.W which resulted in increase of various parameters either to normal or very close to normal value while the rectal temperature and haematocrit decreased non-significantly throughout the observation period of 7 hours. No improvement in Hb and respiration was observed consequent to FM administration. Both treatments successfully raised systolic, diastolic, pulse pressure, C.V.P & M.A.P to normal pre-infusion val-ues. From the results of the present investigation, it can be concluded that i.v. infusion of FM alone and in combination with hypertonic saline solution in en-dotoxemic buffalo calves effectively restores the various hemodynamic parameters close to normal pre-infusion values and it can be used as immediate resuscitation measure to provide the clinician valu-able time to plan further long term treatment.展开更多
The study was conducted to evaluate the safety of Flunixin meglumine injection on target animal dogs, and to provide a scientific basis for the dose selec- tion of clinical application. A total of 24 healthy Springer ...The study was conducted to evaluate the safety of Flunixin meglumine injection on target animal dogs, and to provide a scientific basis for the dose selec- tion of clinical application. A total of 24 healthy Springer Spaniels were randomly divided into four groups. Intramuscular injection of Flunixin meglumine was carried out to test group dogs with the doses of 2 rag/kg, 6 rag/kg, 10 mg/kg for 5 days, respectively. The injected doses were one times, three times and five times as the recommended clinical dose. Intramuscular injection of water was carried out to control group dogs for 5 days. Clinical symptom was observed after the injection, and the blood was collected at different times （before, during and after the injection） to conduct blood routine examination and blood biochemical indexes measurement. Post-mortem examination and histopathological examination were carried out after the test. The results indicated that test dogs showed normal spirit, with no death and no other adverse reactions. Part values of blood routine examination indexes and blood biochemical indexes in test groups showed significant differences between pre-administration and post-administration, but basically fluctuated within the reference range. Autopsy results showed no obvious pathological changes. Histological examination showed the viscera and tissues （liver, heart, spleen, lung, kidney） in high dose group and control group showed no abnormality and pathological changes. The results indicated that Flunixin meglumine injection with the dose of 2 - 10 rag/kg had a minimal effect on physiological and biochemical indexes of dog blood.展开更多
Fifteen apparently healthy male buffalo calves aged between 6 months to one year with body weight range of 70 - 140 Kg divided into 3 groups of 5 buffalo calves each were used in the present investigation. Endotoxic s...Fifteen apparently healthy male buffalo calves aged between 6 months to one year with body weight range of 70 - 140 Kg divided into 3 groups of 5 buffalo calves each were used in the present investigation. Endotoxic shock was produced by IV infusion of Escherichia coli endotoxin @ 5 μg/kg BW/hr for 3 hours followed by administration of three different treatment regimens comprising of intravenous infusion of hypertonic saline solution(HSS) @ 4 ml/Kg bw, flunixin meglumine @ 1.1 mg/Kg bw and blood @ 20 ml/Kg bw to group-I, HSS, Dextran-40 and Flunixin meglumine to group-II and HSS, Dextran-40, whole blood and Flunixin meglumine to group-III with the objectives to study the major physio-pathological changes during induced endotoxemia in buffalo calves and to compare the effects of different treatment options to find out the best treatment option out of the three combinations. All the animals were further observed up to day 2 or death whichever was earlier. Endotoxin infusion to all the animals caused symptoms of restlessness, respiratory distress, snoring, diarrhoea, profuse salivation along with the significant hypoproteinemia, hypoalbuminemia, hypoglobulinemia, hypokalemia and hypocalcemia. The treatment with HSS, flunixin meglumine and blood infused as one time infusion to these endotoxemic buffalo calves not only alleviated the above mentioned symptoms but also significantly raised the circulating albumin level at 5.5 hrs and day 2 and Fibrinogen level at day 2 of observation. A significant hypocalcaemia was observed at 4.5 hours along with an increase in Alkaline Phosphatase at 3.5, 4.5 and 6.5 hrs. All the endotoxemic buffalo calves which died were subjected to post mortem and histopathological studies. Epicardial and endocardial haemorrhages, haemorrhages on intestinal mucosa, congestion, haemorrhages, emphysema and fibrinous thrombi in microvasculature of lungs were salient histopathological findings. On comparison with observations of the other treatment regimens tried, it was found that the IV infusion of展开更多
Six apparently healthy male buffalo calves aged between 6 months to one year with body weight range of 70 - 140 Kg were used in the present investigation. One animal was used for pilot trial for this group. Five calve...Six apparently healthy male buffalo calves aged between 6 months to one year with body weight range of 70 - 140 Kg were used in the present investigation. One animal was used for pilot trial for this group. Five calves were randomly taken into this group. The Eschrechia coli endotoxin infused i/v @5 mg/kg BW/hr for 3 hours to all the animals caused symptoms of restlessness, respiratory distress, snoring, diarrhea, profuse salivation along with the significant fall in systolic, diastolic, pulse and mean arterial venous pressure, hypoproteinemia at 1, 2 & 3 hour and hypoglycemia at 3rd hour i.e., end of endotoxin infusion. Respiration was increased significantly during endotoxin infusion at 2nd & 3rd hour and even afterwards till the end of the observation period i.e. 7 hrs. The treatment with hypertonic saline solution, flunixin meglumine and blood raised (p th, 6th & 7th hour respectively i.e., till the end of the observation period. There was no significant effect on Central Venous Pressure (CVP) and body temperature as measured from rectum.展开更多
Endotoxic shock was induced in five apparently healthy male buffalo calves by i.v infusion of Escherichia coli endotoxin at 5microgram/kilogram (μg/Kg) body weight/hour (BW/hr) for 3 hours. Endotoxin infusion caused ...Endotoxic shock was induced in five apparently healthy male buffalo calves by i.v infusion of Escherichia coli endotoxin at 5microgram/kilogram (μg/Kg) body weight/hour (BW/hr) for 3 hours. Endotoxin infusion caused clinical signs of restlessness, respiratory distress, snoring, diarrhoea, profuse salivation along with the significant hypoproteinemia, hypoalbuminemia and hypokalemia in all the animals. The animals were observed up to day 4 or death, whichever was earlier. The treatment with one time intravenous infusion of hypertonic saline solution @ 4milliliter/Kilogram body weight (ml/Kg?BW), dextran-40 @ 10 ml/Kg?BW, flunixin meglumine @ 1.1 milligram/Kg?BW (mg/Kg?BW) and blood @ 20 ml/Kg?BW to these animals alleviated the clinical signs and significantly raised the circulating glucose level at 4.5 and 5.5 hrs. The treatment led to survival of three of the five endotoxemic buffalo calves. The significant hypoproteinemia, hypoalbuminemia, hypokalemia and hypoglobulinemia continued even after treatment. Gross and histopathologic findings of congestion, haemorrhage, necrosis in vital organs viz., lungs, liver, kidneys, brain and intestines were suggestive of endotoxin induced hypoxia and multi-organ failure. Additionally, emphysema and fibrinous thrombi in microvasculature of lungs were salient histopathological findings indicating terminal respiratory failure in the remaining two dead endotoxemic buffalo calves. From clinical signs, plasma chemistry and pathological lesions, it was concluded that endotoxemia led to a disruption of critical life processes, but a timely and effective treatment could counter these deleterious effects and save precious lives.展开更多
文摘Pharmacokinetics of flunixin meglumine （FM） was investigated in 14 healthy pigs following single intravenous （i.v.） and intramuscular （i.m.） administration of the drug at the dosage of 2.2 and 1.1 mg kg-1. Blood samples were collected at different intervals after administration, and concentrations of FM were determined by HPLC method with a limit of detection of 0.1μg mL-1. The FM concentration-time data were fitted to a two-compartment open model after single i.v. dosing in pigs. The main pharmacokinetic parameters were as follows： tl/2a, 0.49 ± 0.03 and 0.58±0.07 h; tl/2β, 6.28±0.13 and 7.37 ±0.59 h; V/F, 0.01 ±0.001 and 0.01 ±0.002 L kg-1; CL, 0.01 ± 0.002 and 0.01 ± 0.002 L h-l; AUC, 237.73 ± 52.46 and 147.71 ± 36.76μg h-1 mL-1. The drug concentration-time data were fitted to a two-compartment model with first-order absorption after single i.m. administration in pigs. The main pharmacokinetic parameters were as follows： t1/2α, 0.90± 0.07 and 0.86±0.10 h; t1/2β, 8.79±0.85 and 9.60±0.10 h; V/F, 0.02±0.004 and 0.02±0.003 L kg-1; CL, 0.01±0.002 and 0.01 ±0.003 L h-l; AUC, 174.63 ± 45.84 and 112.42 ± 31.19 pg h-1 mL 1. The results of the present study showed that FM was rapidly absorbed, extensively distributed, and slowly eliminated in pigs. The drug was completely absorbed after single i.m. administration and a good bioavailability in pigs.
文摘氟尼辛葡甲铵盐是一种动物专用的非甾体抗炎药,具有镇痛和解热功能,但抗炎是其主要功效。本试验通过对鸡蛋清诱导的大鼠踝关节炎性肿胀模型和冰醋酸所致小鼠疼痛扭体反应来研究其抗炎镇痛效果。与对照组相比,FM高中低各剂量组(0.55、1.1、2.2 m g/kg)对大鼠足关节炎症均有显著的对抗作用(P<0.05,P<0.01),呈明显的量效关系。高剂量组(2.2m g/kg)抗炎功效明显优于吲哚美辛组(2.25 m g/kg)和地塞米松组(2.52 m g/kg)。中剂量组(1.1 m g/kg)作用堪比吲哚美辛,而低剂量组(0.55 m g/kg)稍逊于地塞米松。与同类对照药双氯芳酸钠(16.25 m g/kg)和安乃近(32.5 m g/kg)相比,结果显示FM(2.5 m g/kg)对小鼠扭体抑制作用最强,抑制率高达82.69%。
文摘To investigate the effect of Flunixin meglumine- a NSAID;alone and in combination with hypertonic saline on endotoxemic buffalo calves, two groups of five apparently healthy male buffalo calves aged be-tween 6-8 months were subjected to I.V. infusion of E.coli endotoxin at the rate of 5μg/kg BW per hour for 3 hours. A highly significant (P < 0.01) fall in mean systolic,diastolic, pulse, mean arterial pressure (M.A.P), central venous pressure (C.V.P) and haemo-globin was observed till the end of endotoxin infusion while respiratory rate was significantly elevated along with a non-significant alteration in rectal tem-perature and hematocrit during the infusion of en-dotoxin. Immediately at the end of endotoxin infusion, flunixin meglumine at the rate of 1.1 mg/kg B.W was infused i.v. in group-I animals and group-II animals were infused with hypertonic saline solution (H.S.S.) at the rate of 4 ml/Kg BW as one time infusion fol-lowed by flunixin meglumine at the rate of 1.1 mg/kg B.W which resulted in increase of various parameters either to normal or very close to normal value while the rectal temperature and haematocrit decreased non-significantly throughout the observation period of 7 hours. No improvement in Hb and respiration was observed consequent to FM administration. Both treatments successfully raised systolic, diastolic, pulse pressure, C.V.P & M.A.P to normal pre-infusion val-ues. From the results of the present investigation, it can be concluded that i.v. infusion of FM alone and in combination with hypertonic saline solution in en-dotoxemic buffalo calves effectively restores the various hemodynamic parameters close to normal pre-infusion values and it can be used as immediate resuscitation measure to provide the clinician valu-able time to plan further long term treatment.
文摘The study was conducted to evaluate the safety of Flunixin meglumine injection on target animal dogs, and to provide a scientific basis for the dose selec- tion of clinical application. A total of 24 healthy Springer Spaniels were randomly divided into four groups. Intramuscular injection of Flunixin meglumine was carried out to test group dogs with the doses of 2 rag/kg, 6 rag/kg, 10 mg/kg for 5 days, respectively. The injected doses were one times, three times and five times as the recommended clinical dose. Intramuscular injection of water was carried out to control group dogs for 5 days. Clinical symptom was observed after the injection, and the blood was collected at different times （before, during and after the injection） to conduct blood routine examination and blood biochemical indexes measurement. Post-mortem examination and histopathological examination were carried out after the test. The results indicated that test dogs showed normal spirit, with no death and no other adverse reactions. Part values of blood routine examination indexes and blood biochemical indexes in test groups showed significant differences between pre-administration and post-administration, but basically fluctuated within the reference range. Autopsy results showed no obvious pathological changes. Histological examination showed the viscera and tissues （liver, heart, spleen, lung, kidney） in high dose group and control group showed no abnormality and pathological changes. The results indicated that Flunixin meglumine injection with the dose of 2 - 10 rag/kg had a minimal effect on physiological and biochemical indexes of dog blood.
文摘Fifteen apparently healthy male buffalo calves aged between 6 months to one year with body weight range of 70 - 140 Kg divided into 3 groups of 5 buffalo calves each were used in the present investigation. Endotoxic shock was produced by IV infusion of Escherichia coli endotoxin @ 5 μg/kg BW/hr for 3 hours followed by administration of three different treatment regimens comprising of intravenous infusion of hypertonic saline solution(HSS) @ 4 ml/Kg bw, flunixin meglumine @ 1.1 mg/Kg bw and blood @ 20 ml/Kg bw to group-I, HSS, Dextran-40 and Flunixin meglumine to group-II and HSS, Dextran-40, whole blood and Flunixin meglumine to group-III with the objectives to study the major physio-pathological changes during induced endotoxemia in buffalo calves and to compare the effects of different treatment options to find out the best treatment option out of the three combinations. All the animals were further observed up to day 2 or death whichever was earlier. Endotoxin infusion to all the animals caused symptoms of restlessness, respiratory distress, snoring, diarrhoea, profuse salivation along with the significant hypoproteinemia, hypoalbuminemia, hypoglobulinemia, hypokalemia and hypocalcemia. The treatment with HSS, flunixin meglumine and blood infused as one time infusion to these endotoxemic buffalo calves not only alleviated the above mentioned symptoms but also significantly raised the circulating albumin level at 5.5 hrs and day 2 and Fibrinogen level at day 2 of observation. A significant hypocalcaemia was observed at 4.5 hours along with an increase in Alkaline Phosphatase at 3.5, 4.5 and 6.5 hrs. All the endotoxemic buffalo calves which died were subjected to post mortem and histopathological studies. Epicardial and endocardial haemorrhages, haemorrhages on intestinal mucosa, congestion, haemorrhages, emphysema and fibrinous thrombi in microvasculature of lungs were salient histopathological findings. On comparison with observations of the other treatment regimens tried, it was found that the IV infusion of
文摘Six apparently healthy male buffalo calves aged between 6 months to one year with body weight range of 70 - 140 Kg were used in the present investigation. One animal was used for pilot trial for this group. Five calves were randomly taken into this group. The Eschrechia coli endotoxin infused i/v @5 mg/kg BW/hr for 3 hours to all the animals caused symptoms of restlessness, respiratory distress, snoring, diarrhea, profuse salivation along with the significant fall in systolic, diastolic, pulse and mean arterial venous pressure, hypoproteinemia at 1, 2 & 3 hour and hypoglycemia at 3rd hour i.e., end of endotoxin infusion. Respiration was increased significantly during endotoxin infusion at 2nd & 3rd hour and even afterwards till the end of the observation period i.e. 7 hrs. The treatment with hypertonic saline solution, flunixin meglumine and blood raised (p th, 6th & 7th hour respectively i.e., till the end of the observation period. There was no significant effect on Central Venous Pressure (CVP) and body temperature as measured from rectum.
文摘Endotoxic shock was induced in five apparently healthy male buffalo calves by i.v infusion of Escherichia coli endotoxin at 5microgram/kilogram (μg/Kg) body weight/hour (BW/hr) for 3 hours. Endotoxin infusion caused clinical signs of restlessness, respiratory distress, snoring, diarrhoea, profuse salivation along with the significant hypoproteinemia, hypoalbuminemia and hypokalemia in all the animals. The animals were observed up to day 4 or death, whichever was earlier. The treatment with one time intravenous infusion of hypertonic saline solution @ 4milliliter/Kilogram body weight (ml/Kg?BW), dextran-40 @ 10 ml/Kg?BW, flunixin meglumine @ 1.1 milligram/Kg?BW (mg/Kg?BW) and blood @ 20 ml/Kg?BW to these animals alleviated the clinical signs and significantly raised the circulating glucose level at 4.5 and 5.5 hrs. The treatment led to survival of three of the five endotoxemic buffalo calves. The significant hypoproteinemia, hypoalbuminemia, hypokalemia and hypoglobulinemia continued even after treatment. Gross and histopathologic findings of congestion, haemorrhage, necrosis in vital organs viz., lungs, liver, kidneys, brain and intestines were suggestive of endotoxin induced hypoxia and multi-organ failure. Additionally, emphysema and fibrinous thrombi in microvasculature of lungs were salient histopathological findings indicating terminal respiratory failure in the remaining two dead endotoxemic buffalo calves. From clinical signs, plasma chemistry and pathological lesions, it was concluded that endotoxemia led to a disruption of critical life processes, but a timely and effective treatment could counter these deleterious effects and save precious lives.
