Flunixin Administration Research Articles

Impact of transdermal flunixin administration on serum prostaglandin E2 and cortisol concentrations in piglets following castration

To assess the effects of transdermal flunixin administration on serum prostaglandin E2 (PGE2) and cortisol concentrations in piglets undergoing castration. 104 litters with at least 4 male piglets/litter. Litters were randomly assigned to 1 of 4 treatments: transdermal flunixin (3.33 mg/kg) administration followed by surgical castration (CF; n = 28), transdermal flunixin administration followed by sham castration (SF; n = 26), application of physiologic saline solution followed by sham castration (S; n = 26), and application of physiologic saline solution followed by surgical castration (C; n = 24). Blood samples were collected 24 hours before and 1, 4, and 25 hours after castration or sham castration. Serum PGE2 concentrations for piglets in the C and CF groups did not differ at any time. Piglets in the S group tended to have higher serum PGE2 concentrations 1 hour after sham castration compared with piglets in the SF group. One hour after the procedure, piglets that underwent castration had higher serum cortisol concentrations than did piglets that underwent sham castration. Piglets in the CF group had higher serum cortisol concentrations than did piglets in the SF group 4 hours after the procedure, but serum cortisol concentrations did not differ between the C and S groups. Further studies are needed to explore dosing regimens, including effective doses and administration frequencies, and the pharmacokinetics of flunixin following transdermal administration in piglets undergoing castration.

Medication control of flunixin in racing horses: Possible detection times using Monte Carlo simulations.

SummaryBackgroundFor medication control in several jurisdictions, withdrawal time is the period of refrain from racing after drug administration. It is set by adding a safety period to an experimental detection time. However, there are no reports of statistical analyses of detection time for the determination of withdrawal time in flunixin meglumine‐treated horses.ObjectiveTo analyse the population pharmacokinetics of flunixin in horses through the generation of a dataset for detection time statistical analysis and predictions via Monte Carlo simulation.Study designExperimental study.MethodsDrug plasma and urine concentrations following single intravenous administration of flunixin 1.1 mg/kg bodyweight (BW) in 10 horses and multiple administration of q 24 hours for 5 days in 10 horses were measured using liquid chromatography with tandem mass spectrometry (LC‐MS/MS). Data were modelled using a nonlinear mixed effect model followed by Monte Carlo simulation. Irrelevant plasma concentration (IPC) and irrelevant urine concentration (IUC) were calculated using the Toutain approach. Detection times were obtained considering the time after the last administration for selected quantiles of 5000 hypothetical horses under the international screening limit (ISL) proposed by the International Federation of Horseracing Authorities (plasma: 1 ng/mL, urine; 100 ng/mL).ResultsFor a regimen of 1.1 mg/kg BW q 24 hours, the IPC and IUC values were 2.0 and 73.0 ng/mL respectively. Detection times in plasma above the ISL for 90% of simulated horses were estimated as 74 hours after a single 1.1 mg/kg dose administration, 149 and 199 hours after multiple doses over 5 days at either 24‐ or 12‐hour intervals respectively. Corresponding detection times in urine were 46, 68 and 104 hours respectively.Main limitationOnly female horses were investigated.ConclusionsStatistical detection times for different flunixin meglumine regimens indicated a delay of detection time in plasma after multiple administrations under ISL.

A retrospective study of twin pregnancy management in mares

The aim of the study was to compare three methods of reducing twin pregnancy in mares to maintain a single pregnancy. As multiple pregnancies in mare are always undesirable, early ultrasound diagnosis makes possible management of twin pregnancies and extra embryo removal. In years 2010–2018, 16494 mares were sonographically tested for early pregnancy, finding 868 cases of twins (471 bilateral and 397 unilateral). 260 mares with a confirmed bilateral tween pregnancy were subjected to manual crushing of one embryo and administration of flunixin at a dose of 1.1 mg/kg BW. 186 mares were subjected only to the embryo crushing procedure. 25 mares from this group were on a restrictive diet. In the unilateral twin pregnancy mare group, 62 were subjected to manual embryo reduction with simultaneous treatment with flunixin, 60 had only manual embryonic vesicle crush and 210 had a restrictive diet. Determination of success, measured as the development of a single pregnancy, were monitored 2 weeks after the procedure, between the 50th and 60th day of pregnancy and after the 90th day of pregnancy. In general, warm-blooded mares were more prone to a twin pregnancy, and at the same time, all the procedures used to reduce it to a single pregnancy caused a greater risk of losing both embryos than in the case of cold-blooded mares. The beneficial effect of administering flunixin after manual removal of one embryo on the maintenance of the other has been experimentally proven in both unilateral and bilateral twin pregnancy.

Short communication: Determination of the milk pharmacokinetics and depletion of milk residues of flunixin following transdermal administration to lactating Holstein cows

Flunixin is a nonsteroidal anti-inflammatory drug and the most commonly prescribed analgesic in cattle in the United States. Recently, the US Food and Drug Administration (FDA) approved a transdermal formulation of flunixin for control of pyrexia associated with bovine respiratory disease and the control of pain associated with foot rot. The transdermal formulation is not currently approved for use in lactating dairy cattle in the United States, but extra-label use in dairy cattle is permissible under US regulations. The objectives of this study were to determine the pharmacokinetics in milk of dairy cows treated with transdermal flunixin and determine an appropriate withdrawal time for milk. Ten lactating Holstein cows were enrolled into the study in mid lactation. Following treatment, cows were milked 3 times per day through 144 h. Milk samples were collected for drug analysis using ultra-high-pressure liquid chromatography coupled with a triple quadrupole mass spectrometer. The geometric mean maximum concentration for flunixin in milk was 0.010 μg/mL and was 0.061 μg/mL for the active metabolite, 5-hydroxyflunixin. The geometric mean terminal half-life was 20.71 h for flunixin and 22.62 h for 5-hydroxyflunixin. Calculations to approximate a withdrawal time in milk following transdermal flunixin administration were accomplished using a statistical tolerance limit procedure. This analysis indicated that it would be prudent to observe a withdrawal period of 96 h following the last treatment. This is more than twice as long as the labeled withdrawal period of 36 h following use of the injectable formulation. The withdrawal period suggested by this work should be applied carefully, as this study was not conducted under the full quality control practices required by the US FDA for a full drug approval study. Caution should be taken when applying this withdrawal time to diseased animals, animals that are milked with different milking frequencies, and those in different stages of production as these have all been shown to affect drug depletion from milk.

Effect of age on the pharmacokinetics and pharmacodynamics of flunixin meglumine following intravenous and transdermal administration to Holstein calves.

OBJECTIVE To determine the effect of age on the pharmacokinetics and pharmacodynamics of flunixin meglumine following IV and transdermal administration to calves. ANIMALS 8 healthy weaned Holstein bull calves. PROCEDURES At 2 months of age, all calves received an injectable solution of flunixin (2.2 mg/kg, IV); then, after a 10-day washout period, calves received a topical formulation of flunixin (3.33 mg/kg, transdermally). Blood samples were collected at predetermined times before and for 48 and 72 hours, respectively, after IV and transdermal administration. At 8 months of age, the experimental protocol was repeated except calves received flunixin by the transdermal route first. Plasma flunixin concentrations were determined by liquid chromatography-tandem mass spectroscopy. For each administration route, pharmacokinetic parameters were determined by noncompartmental methods and compared between the 2 ages. Plasma prostaglandin (PG) E2 concentration was determined with an ELISA. The effect of age on the percentage change in PGE2 concentration was assessed with repeated-measures analysis. The half maximal inhibitory concentration of flunixin on PGE2 concentration was determined by nonlinear regression. RESULTS Following IV administration, the mean half-life, area under the plasma concentration-time curve, and residence time were lower and the mean clearance was higher for calves at 8 months of age than at 2 months of age. Following transdermal administration, the mean maximum plasma drug concentration was lower and the mean absorption time and residence time were higher for calves at 8 months of age than at 2 months of age. The half maximal inhibitory concentration of flunixin on PGE2 concentration at 8 months of age was significantly higher than at 2 months of age. Age was not associated with the percentage change in PGE2 concentration following IV or transdermal flunixin administration. CONCLUSIONS AND CLINICAL RELEVANCE In calves, the clearance of flunixin at 2 months of age was slower than that at 8 months of age following IV administration. Flunixin administration to calves may require age-related adjustments to the dose and dosing interval and an extended withdrawal interval.

Distribution of Flunixin Residues in Muscles of Dairy Cattle Dosed with Lipopolysaccharide or Saline and Treated with Flunixin by Intravenous or Intramuscular Injection.

Twenty dairy cows received flunixin meglumine at 2.2 mg/kg bw, administered once daily by either the intravenous (IV) or intramuscular (IM) route for three consecutive days with either intravenous normal saline (NS) or lipopolysaccharide (LPS) providing a balanced design with five animals per group. Cows were sacrificed after a 4 day withdrawal period, and 13 muscle types were collected and assayed for flunixin by LC-MS/MS. After elimination of sample outliers, the main effects of route of administration (IV or IM), treatment (NS or LPS), and tissue type significantly (P < 0.05) affected flunixin residues, with no interaction (P > 0.05). Intramuscular (nonlabel) flunixin administration produced greater (P < 0.05) flunixin residues in muscle than the IV (label) administration, whereas LPS resulted in lower flunixin levels. Differences among the tissue levels indicate it is necessary to specify the tissue to be used for any monitoring of drug levels for consumer protection.

Preliminary Study on the Effect of Flunixin Administration on Pharmacokinetics of Cefquinome in Diseased Cattle Calves

Cefquinome is one of the fourth generations of cephalosporins developed for veterinary use in treatment of respiratory diseases that are considered the second causes of death in calves. Non-steroidal anti-inflammatory drugs such as flunixin (NSAIDs) are widely prescribed with antibacterial agents in multiple drug prescriptions. The present study aimed to investigate the effect of co-administration of flunixin on the disposition kinetics of cefquinome after intramuscular injection in 10 diseased calves (Pasturella heamolytica infected). Cefquinome was injected in a single dose (2 mg/kg BW) in 5 diseased calves alone and coupled with flunixin (1mg/kg BW) in the other 5 diseased calves. Blood samples (5 mL) were collected from the right jugular vein of each calve immediately before treatment and at intervals of 0, 5, 10, 15 and 30 min, 1, 2, 4, 6, 8, 12, and 24 hours, 48, 72, 96 and 120 h (5 days) after cefquinome administration. The obtained samples were assayed with the plate microbiological assay method using Sarcina lutea (ATCC 9341) as test organism. The plasma cefquinome concentration at 5 min after intramuscular injection of cefquinome alone and coupled with flunixin was 0.27 ± 0.05 μg/mL and 0.35 ± 0.12 μg/mL, respectively and reached the highest concentration (1.02 ± 0.12 μg/mL and 1.02 ± 0.08 μg/mL) at 1 h, respectively. The obtained data showed no significant effect of coupled administration of flunixin with cefquinome on either concentration or peak concentration of cefquinome in plasma of diseased calves. It is concluded that flunixin can be used successfully with cefquinome in treatment of bacterial respiratory diseases associated with inflammation in calves.

Effect of local infusion of NSAID analgesics administered alone or in combination on the pain associated with band castration in calves.

To evaluate the analgesic efficacy of flunixin alone or in combination with diclofenac administered locally to the scrotum at the time of band castration of calves. Angus bull calves (n = 40; ≈7-9 weeks old) were allocated to four treatment groups (n = 10 per group) to examine the effects of two non-steroidal anti-inflammatory analgesics (NSAIDs) administered locally at the time of band castration: sham control; castration + flunixin; castration + flunixin + diclofenac; castration + saline. The NSAIDs and saline were administered subcutaneously into the scrotum under the band. Blood was sampled at -0.5, 0.5, 1.5, 3, 12, 24, 48 and 72 h relative to castration. Haematology parameters and plasma cortisol levels were determined in samples at all time points and plasma haptoglobin levels determined in samples collected at -0.5, 24, 48 and 72 h. Pain avoidance and postural behaviours were measured for 2 and 12 h, respectively, after castration. Band-castrated calves exhibited significantly higher peak cortisol and higher integrated cortisol responses during the first 6 h post-castration relative to sham controls. Individual active pain avoidance behaviours observed for 1 h post-castration were not significantly different between treatment groups; however; the sum of the total behaviours was significantly increased by castration (P = 0.023). Postural changes included increased abnormal ventral lying for all castrated groups and decreased normal standing and increased combined abnormal postures for the flunixin- and saline-treated groups. Growth rates of calves were not affected by treatments during weeks 1 and 2 post-castration; however, growth rates of castrated calves were significantly lower than those of sham-treated calves in week 3 post-castration (1.41 vs 0.84, 0.75 and 0.56±0.19 kg/day for sham, flunixin-, flunixin + diclofenac- and saline-treated groups, respectively). The administration of flunixin or flunixin + diclofenac intrascrotally at several sites at the time of banding did not improve the welfare of young Angus bull calves undergoing this method of castration when assessed by both physiological and behavioural parameters. In this study, band castration at 7-9 weeks of age had less effect compared with results for older calves reported previously. Further research is required to develop effective analgesic treatments that can be administered at the time of castration to large numbers of animals.

Excretory, Secretory, and Tissue Residues after Label and Extra-label Administration of Flunixin Meglumine to Saline- or Lipopolysaccharide-Exposed Dairy Cows.

Twenty lactating dairy cattle were intravenously infused with either lipopolysaccharide (LPS) (n = 10) or sterile saline (n = 10). Five cattle in each group received three doses of flunixin meglumine administered by either intravenous infusion or intramuscular injection at 24 h intervals. Milk, urine, and tissues were collected. Thirty-six hours after the last flunixin administration, milk from six cows contained 5-hydroxyflunixin (5OHF) levels greater than the milk tolerance of 2 ng/mL; by 48 h, milk from two cows, a saline and a LPS-treated animal, had violative milk concentrations of 5OHF. A single animal treated with LPS and intramuscular flunixin contained violative flunixin residues in liver. The ratio of urinary flunixin/5OHF was correlated (P < 0.01; R(2) = 0.946) with liver flunixin residues in LPS-treated animals, but not (P = 0.96; R(2) = 0.003) in cows treated with saline in lieu of LPS. Violative residues of flunixin in dairy cattle may be related to LPS inhibition of flunixin metabolism.

Different Methods to Identify Pain after Routine Surgical Castration of Equine Stallions: Composite Pain Scale, Facial Expressions, Faecal Glucocorticoid Metabolites and Plasma Cytokines

Reasons for performing studyLack of ‘gold standard’ for pain assessment in horses.ObjectivesTo assess different approaches of quantifying pain in horses. Castration was chosen as a pain model because of its wide clinical relevance.Study designExploratory study.Methods51 equine stallions undergoing castration under general anaesthesia were divided in 3 pain‐relieving treatment groups: A) single perioperative administration of flunixin (n = 19), B) additional subsequent flunixin administrations (n = 21), D) like A but with intra‐operative mepivacaine injections into the spermatic cord (n = 11). All horses were assessed before and 5 times after surgery (up to 44 h) by means of a modified composite pain scale (CPS), a newly developed facial expression pain scale (FEPS), faecal glucocorticoid metabolites (GCMs) and plasma cytokine profiles. The same parameters were measured in a control group C, undergoing general anaesthesia for different nonpainful procedures (n = 6). Data were analysed with nonparametric statistical tests (Wilcoxon, Mann Whitney U).ResultsTime had an influence on CPS and FEPS scores in treatment groups A, B and D but not in C. Scores of groups A and B were higher compared to groups D and C at 4 (CPS, FEPS) and 8 h (CPS), whereas there was no difference between groups A and B nor between groups D and C. Only in group AB was there an increase of faecal GCMs 20 h after surgery. GCMs in group AB were higher compared with groups C and D at 32 h. No effects by time or treatment could be identified for the different plasma cytokines.ConclusionsCPS and FEPS seem to be able to detect different levels of post castration pain differentiating from possible anaesthesia effect. Additional local anaesthesia of the spermatic cord was associated with lower post surgical pain scores when compared to perioperative flunixin application alone, whereas subsequent applications of flunixin had no obvious effect.Ethical animal research: This study was registered as an animal experiment by the Brandenburg state authority (V3‐2347‐A‐42‐1‐2012). Client‐owned horses were included with informed consent. Sources of funding: EU‐funded FP7‐project “Animal Welfare Indicators (AWIN)” (FP7‐KBBE‐2010‐4). Competing interests: None.

Plasma pharmacokinetics and milk residues of flunixin and 5-hydroxy flunixin following different routes of administration in dairy cattle

The objective of this study was to determine if the plasma pharmacokinetics and milk elimination of flunixin (FLU) and 5-hydroxy flunixin (5OH) differ following intramuscular and subcutaneous injection of FLU compared with intravenous injection. Twelve lactating Holstein cows were used in a randomized crossover design study. Cows were organized into 2 groups based on milk production (<20 or >30kg of milk/d). All cattle were administered 2 doses of 1.1mg of FLU/kg at 12-h intervals by intravenous, intramuscular, and subcutaneous injections. The washout period between routes of administration was 7d. Blood samples were collected from the jugular vein before FLU administration and at various time points up to 36h after the first dose of FLU. Composite milk samples were collected before FLU administration and twice daily for 5d after the first dose of FLU. Samples were analyzed by ultra-HPLC with mass spectrometric detection. For FLU plasma samples, a difference in terminal half-life was observed among routes of administration. Harmonic mean terminal half-lives for FLU were 3.42, 4.48, and 5.39h for intravenous, intramuscular, and subcutaneous injection, respectively. The mean bioavailability following intramuscular and subcutaneous dosing was 84.5 and 104.2%, respectively. The decrease in 5OH milk concentration versus time after last dose was analyzed with the nonlinear mixed effects modeling approach and indicated that both the route of administration and rate of milk production were significant covariates. The number of milk samples greater than the tolerance limit for each route of administration was also compared at each time point for statistical significance. Forty-eight hours after the first dose, 5OH milk concentrations were undetectable in all intravenously injected cows; however, one intramuscularly injected and one subcutaneously injected cow had measurable concentrations. These cows had 5OH concentrations above the tolerance limit at the 36-h withdrawal time. The high number of FLU residues identified in cull dairy cows by the United States Department of Agriculture Food Safety Inspection Service is likely related to administration of the drug by an unapproved route. Cattle that received FLU by the approved (intravenous) route consistently eliminated the drug before the approved withdrawal times; however, residues can persist beyond these approved times following intramuscular or subcutaneous administration. Cows producing less than 20kg of milk/d had altered FLU milk clearance, which may also contribute to violative FLU residues.

Pharmacokinetic study of flunixin and its interaction with enrofloxacin after intramuscular administration in calves

The Pharmacokinetic aspects of flunixin (FL) administered alone and in combination with enrofloxacin (EN), were studied in clinically healthy calves. The experiments were performed on two groups: FL alone {2.2 mg/kg,intramuscular (IM)}, and combination of FL (2.2 mg/kg, IM) and EN {2.5 mg/kg, IM}. Plasma concentrations of FL were determined using High Performance Liquid Chromatography (HPLC) method. Moreover, the effects of FL alone or in combination on liver and kidney functions were also assessed. Flunixin was rapidly absorbed intramuscularly with a half-life of absorption (t ) of 0.094 h and the peak plasma concentration (C ) was 1.27 g/mL was attained after 1/2ab max 0.49 h (T ). Enrofloxacin significantly altered the pharmacokinetics of FL by delaying its absorption and accelerate its max elimination from body. Significant increases (32%) in the area under the curve (AUC) and (37%) in the elimination rate constant (K ) from the central compartment and a significant decrease (27%) in the elimination half-life (t ) of FL el 1/2el were found following coadministration with EN, compared with administration of FL alone. The maximum plasma drug concentration (C ) showed significant increase (28%) following the coadministration of EN with FL as max compared to that following the administration of FL alone. It was concluded that the combination of FL and EN negatively altered the kinetics of FL and exaggerated the adverse effect on hepato-renal function in calves consequently; the concomitant use of FL and EN should be avoided in calves.

Effects of Acute Hepatic and Renal Failure on Pharmacokinetics of Flunixin Meglumine in Rats

The aim of this study was to investigate the effects of hepatic and renal failure on the pharmacokinetics of flunixin in carbon tetrachloride (CCl(4))- and glycerol-treated rats. After intravenous administration of flunixin (2 mg/kg), the plasma concentration of flunixin was measured by high-performance liquid chromatography. Both acute hepatic and renal failure resulted in significantly increased area under the curve (AUC), prolonged elimination half-life (t(1/2β)), and reduced total body clearance (Cl(tot)) compared with respective controls (P<0.05). In conclusion, hepatic failure as well as renal failure modified the pharmacokinetics of flunixin.

Pharmacokinetic Interactions of Flunixin Meglumine and Enrofloxacin in ICR Mice

We examined the pharmacokinetic interactions of enrofloxacin and flunixin in male ICR mice that were subcutaneously (SC) administered with both or either one of the drugs. The experiments were performed on the following three groups: flunixin alone (2 mg/kg, SC), combination of flunixin (2 mg/kg, SC) and enrofloxacin (10 mg/kg, SC), and enrofloxacin alone (10 mg/kg, SC). Blood samples were collected at 5, 15 and 30 min, and 1, 2, 3, 4, 5 and 6 h after the drug administration, and the pharmacokinetic parameters of flunixin and enrofloxacin were evaluated from the plasma drug concentrations. Significant changes were detected in the pharmacokinetics of flunixin following its coadministration with enrofloxacin. Coadministration of flunixin and enrofloxacin resulted in a 41% increase of the area under the curve (AUC) and a 53% extension of the terminal half-life of flunixin; moreover, flunixin attained the maximum plasma drug concentration 2.75 times faster than when administered alone. The terminal rate constant and the maximum plasma drug concentration showed significant decreases of 34% and 33%, respectively, following the coadministration of enrofloxacin and flunixin as compared to those following the administration of flunixin alone. In contrast, no significant difference in the pharmacokinetics of enrofloxacin was detected following its coadministration with flunixin, as compared to those following the administration of enrofloxacin alone. Following the administration of enrofloxacin alone or its coadministration with flunixin, the plasma level of ciprofloxacin, the metabolite of enrofloxacin, was very low or undetectable. In conclusion, the pharmacokinetics of flunixin in ICR mice are altered by the coadministration of flunixin and enrofloxacin.

Pharmacokinetic interactions of flunixin meglumine and enrofloxacin in dogs

To examine pharmacokinetic interactions of flunixin meglumine and enrofloxacin in dogs following simultaneously administered SC injections of these drugs. 10 Beagles (4 males and 6 females). All dogs underwent the following 3 drug administration protocols with a 4-week washout period between treatments: flunixin administration alone (1 mg/kg, SC); simultaneous administration of flunixin (1 mg/kg, SC) and enrofloxacin (5 mg/kg, SC); and enrofloxacin administration alone (5 mg/kg, SC). Blood samples were collected from the cephalic vein at 0.5, 0.75, 1, 1.5, 2, 3, 5, 8, 12, and 24 hours following SC injections, and pharmacokinetic parameters of flunixin and enrofloxacin were calculated from plasma drug concentrations. Significant increases in the area under the curve (32%) and in the elimination half-life (29%) and a significant decrease (23%) in the elimination rate constant from the central compartment of flunixin were found following coadministration with enrofloxacin, compared with administration of flunixin alone. A significant increase (50%) in the elimination half-life and a significant decrease (21%) in the maximum plasma drug concentration of enrofloxacin were found following coadministration with flunixin, compared with administration of enrofloxacin alone. The observed decrease in drug clearances as a result of coadministration of flunixin and enrofloxacin indicates that these drugs interact during the elimination phase. Consequently, care should be taken during the concomitant use of flunixin and enrofloxacin in dogs to avoid adverse drug reactions.

Pharmacokinetics and Pharmacodynamic Effects of Flunixin after Intravenous, Intramuscular and Oral Administration to Dairy Goats

The pharmacokinetics and the prostaglandin (PG) synthesis inhibiting effect of flunixin were determined in 6 Norwegian dairy goats. The dose was 2.2 mg/kg body weight administered by intravenous (i.v.), intramuscular (i.m.) and oral (p.o.) routes using a cross-over design. Plasma flunixin content was analysed by use of liquid chromatography and the PG synthesis was evaluated by measuring plasma 15-ketodihydro-PGF2α by a radioimmuno-assay. Results are presented as median (range). The elimination half-lives (t1/2·λ) were 3.6 (2.0–5.0), 3.4 (2.6–6.8) and 4.3 (3.4–6.1) h for i.v., i.m. and p.o. administration, respectively. Volume of distribution at steady state (Vdss) was 0.35 (0.23–0.41) L/kg and clearance (CL), 110 (60–160) mL/h/kg. The plasma concentrations after oral administration showed a double-peak phenomenon with the two peaks occurring at 0.37 (0.25–1) and 3.5 (2.5–5.0) h, respectively. Both peaks were in the same order of magnitude. Bioavailability was 79 (53–112) and 58 (35%–120)% for i.m. and p.o. administration, respectively. 15-Ketodihydro-PGF2α plasma concentrations decreased after flunixin administration independent of the route of administration.

Disposition of sodium salicylate, flunixin and meloxicam after intravenous administration in broiler chickens.

Three nonsteroidal anti-inflammatory drugs (NSAIDs) [sodium salicylate, flunixin (FLU) and meloxicam (MEL)] were administered intravenously to broiler chickens. Plasma concentrations were determined by high-performance liquid chromatography methods and pharmacokinetic parameters were calculated. After intravenous administration of sodium salicylate (50 mg/kg), FLU (1.1 mg/kg) and MEL (0.5 mg/kg), these drugs were eliminated from plasma with a mean half-life of 04.04, 05.45 and 03.20 h, respectively. Apparent volumes of distribution (0.39, 0.08 and 0.12 L/kg, respectively) indicated that tissue distribution was limited for the three drugs. Total body clearance was 70 mL/h.kg for sodium salicylate and 10 and 25 mL/kg.h for FLU and MEL, respectively. Based on the pharmacokinetic parameters these NSAIDs may offer possibilities for treatment of various conditions in chickens.

Pharmacodynamics of flunixin and ketoprofen in mallard ducks (Anas platyrhynchos).

Flunixin (FLX) and ketoprofen (KET) are potent nonsteroidal anti-inflammatory drugs (NSAIDs) used to alleviate pain and decrease inflammation. These drugs block access of arachidonic acid to its binding site on the cyclooxygenase enzyme, thus preventing conversion to thromboxane A2 and subsequent degradation to thromboxane B2 (TBX). Consequently, plasma TBX may be used to estimate duration of NSAID action. Sixteen adult mallard ducks (Anas platyrhynchos) were randomly assigned to three treatment groups: control (n = 4), FLX 5 mg/kg (n = 6), or KET 5 mg/kg (n = 6). Blood samples were taken 1 hr prior to and just before (0 hr) injection and 0.25, 0.5, 1, 2, 4, 6, 12, 24, 36, and 48 hr after injection. Plasma samples were analyzed for corticosterone and TBX. The feces were tested for the presence of hemoglobin and the ducks were euthanized for complete necropsy at the end of the study. Samples of muscle, kidney, liver, proventriculus, and intestine were taken for histologic analysis. Thromboxane was suppressed significantly in all birds following administration of either FLX or KET for 4 hr and decreased for approximately 12 hr compared with baseline samples (-1 and 0 hr). In the control group, TBX gradually declined over time. None of the ducks showed evidence of gastrointestinal bleeding, but the FLX group had muscle necrosis present at injection sites. FLX and KET likely exert pharmacological effects for at least 12 h. Although degree of TBX inhibition cannot be correlated absolutely with degree of analgesia or anti-inflammatory effects, it is possible that these effects are present during this time. This work suggests that FLX and KET can potentially be used as anti-inflammatory and analgesic agents in waterfowl. However, because of muscle necrosis at the injection site, we do not recommend parenteral use of FLX in ducks.

β-endorphin immunoreactivity during anaesthesia in equidae

To determine the effects of surgery, hypoxia, hypercapnia and flunixin administration on plasma β-endorphin immunoreactivity (BEI) in anaesthetized horses. Prospective crossover study. Six healthy adult Welsh Mountain ponies and seven healthy adult Thoroughbreds. Ponies were anaesthetized with thiopentone and halothane or with pentobarbitone and the horses with guaiphenesin, thiopentone and halothane. Ponies were anaesthetized for 2 hours and on separate occasions underwent a period of hypoxia, hypercapnia, anaesthesia only, or were given flunixin at induction. The horses were anaesthetized for 2 hours and on separate occasions underwent surgery to relocate one carotid artery subcutaneously or anaesthesia only. Plasma samples were taken pre-anaesthesia, at 20 minute intervals during, and after anaesthesia for BEI assay using radio-immunoassay. Analysis of variance of the concentration-time curve was used for statistical analysis. Pre-anaesthetic β-endorphin immunoreactivity (BEI) values ranged between 5.7 and 20.4 pmol L-1. Induction of anaesthesia caused a five to 10 fold increase in mean plasma BEI in all cases except the hypercapnia group. Halothane anaesthesia increased BEI in ponies and horses but there were no significant changes during pentobarbitone anaesthesia. The increase in BEI in the hypoxic group was greater (peak value 136.8 ± 32.2 pmol L-1) and sustained for a longer period compared with levels in those given halothane alone or in those which became hypercapnic. There was marked individual variation in the flunixin group and changes were not significant. Surgery in the horses resulted in the highest peak values in the study (182.5 ± 153.0 pmol L-1) but the AUC was not significantly higher than in the same animals without surgery, where the peak value was 102.9 ± 42.1 pmol L-1. CONCLUSIONS: Beta-endorphin appeared to be a sensitive marker of an endocrine stress response but its physiological role during equine anaesthesia is unknown. Unknown.

The effect of oral administration of flunixin on luteolysis in heifers

The effect of oral administration of flunixin on luteolysis in heifers