Chronic flunixin meglumine therapy in foals

Effects of a therapeutic dose of flunixin meglumine on gastric mucosa of horse foals were determined by endoscopy, double-contrast radiography, and gross and histologic examinations. Foals were administered 1.1 mg of flunixin meglumine/kg of body weight, PO/day for 30 days in an encapsulated form that was divided into 2 doses/day (group 1; n = 3) or by IM injection once a day (group 2; n = 7). Three control foals (group 3; n = 3) were administered capsules (n = 1) containing dextrose powder or IM injections (n = 2) of vehicle solution without flunixin meglumine. All 3 groups-1 foals given flunixin meglumine PO developed oral ulcers. Group-2 foals given flunixin meglumine IM did not develop oral ulcers. One control foal (group 3) developed 1 oral ulcer that healed during the study. Endoscopic examination revealed linear crease-like mucosal lesions in the glandular portion of the stomach in 2 group-2 foals. Radiographic evidence of gastric ulcers was observed in only 1 gastrogram of a group-1 foal. Foals were euthanatized, and necropsy revealed erosions and/or ulcers of the glandular portion of the stomach. Oral ulcers were observed in all 3 group-1 foals. Erosions of the glandular portion of the stomach developed in all 10 foals given flunixin meglumine, but did not develop in group-3 foals. Ulceration of the glandular portion of the stomach was present in 1 group-2 foal.     

Effects of flunixin and flunixin plus prednisone on the gastrointestinal tract of dogs

Flunixin meglumine has been reported to induce gastrointestinal lesions in dogs when administered at therapeutic dosages. We administered flunixin meglumine to dogs daily for 10 days to assess the effect of this drug on the gastrointestinal tract. We also evaluated the possibility of corticosteroid potentiation of gastrointestinal toxicosis by concurrent administration of prednisone to 1 group of dogs. Dogs were monitored for gastrointestinal toxicosis by means of serial endoscopic evaluation, measurement of fecal occult blood, PCV, and total solid concentration, and by physical examination. There were 3 treatment groups of 5 dogs each. Group-1 dogs were given 2.2 mg of flunixin meglumine/kg daily, in 2 divided doses IM; group-2 dogs were given 4.4 mg of flunixin meglumine/kg daily, in 2 divided doses IM; and group-3 dogs were given 2.2 mg of flunixin meglumine/kg daily, in 2 divided doses IM plus 1.1 mg of prednisone/kg/d orally, in 2 divided doses. A fourth group of 5 dogs served as a control group. Endoscopically visible gastric mucosal lesions developed in all treated dogs within 4 days of initiating treatment. Lesions first developed in the gastric pylorus and antrum and lesions at these sites were more severe than those observed elsewhere. Dogs treated with flunixin meglumine plus prednisone developed the earliest and most severe lesions; lesion scores in group-2 dogs were higher than those in group-1 dogs. All dogs treated had occult blood in their feces by day 5 and its presence appeared to correlate more closely with endoscopic findings than did physical examination findings or changes in values for PCV or total solids.(ABSTRACT TRUNCATED AT 250 WORDS)     

Evaluation of flunixin meglumine as an adjunct treatment for diarrhea in dairy calves

OBJECTIVE: To assess the use of flunixin meglumine as an adjunct treatment for diarrhea in calves. DESIGN: Clinical trial. ANIMALS: 115 calves with diarrhea that were 1 to 21 days old at enrollment. PROCEDURE: Calves that developed diarrhea were randomly assigned to receive no flunixin meglumine (controls), a single dose of flunixin meglumine (2.2 mg/kg [1.0 mg/lb]), or 2 doses of flunixin meglumine administered 24 hours apart. Serum IgG concentration and PCV were measured prior to enrollment in the trial. Calves were evaluated daily to determine rectal temperature, fecal consistency, demeanor, and skin elasticity score. The primary analytic outcome was days of sickness (morbid-days). RESULTS: Calves with fecal blood and treated with a single dose of flunixin meglumine had fewer morbid-days and antimicrobial treatments, compared with controls. Although not significant, calves given 2 doses of flunixin meglumine in 24 hours had fewer morbid-days than untreated control calves. Regardless of severity of diarrhea, calves without fecal blood did not benefit from the use of flunixin. For calves with fecal blood, failure of passive transfer (low serum IgG concentration) was an independent risk factor for increased morbid-days. CONCLUSIONS AND CLINICAL RELEVANCE: Treatment with a single dose of flunixin meglumine resulted in fewer antimicrobial treatments and morbid-days in calves with fecal blood. As observed in other studies, calves with failure of passive transfer were at high risk for poor outcomes. This emphasizes the importance of developing and implementing effective colostrum delivery programs on dairy farms.     

Hemodynamics, plasma eicosanoid concentrations, and plasma biochemical changes in calves given multiple injections of Escherichia coli endotoxin

Twelve male neonatal calves (39 to 50 kg) were allotted to 3 groups of 4 calves each. All calves were anesthetized with halothane, and then Escherichia coli endotoxin was given intravenously (3 times) and intraperitoneally (3 times) during a 6-hour period. Group-1 calves were untreated, group-2 calves were pretreated with a low dose of flunixin meglumine (1.1 mg/kg of body weight), and group-3 calves were pretreated with a high dose of flunixin meglumine (4.4 mg/kg). In calves of group 1, the mean systemic arterial blood pressure (MABP) and cardiac output (CO) decreased, but pulmonary arterial pressure increased after the initial intravenous and intraperitoneal injections of endotoxin. In calves of this group, these changes were accompanied by increased plasma thromboxane B2 (TxB2) concentration. During this period, increased plasma TxB2 concentration or hemodynamic changes were not detected in calves of groups 2 and 3. Only calves of group 1 had altered hemodynamics early in the experiment; however, after 6 hours, calves of all 3 groups had similarly decreased CO and MABP. In calves of the untreated group, plasma 6-keto-prostaglandin (PG)F1 alpha concentration increased steadily from the beginning of the experiment until 3 hours later. The CO and MABP were low at the time when serum 6-keto-PGF1 alpha concentration was high; however, these 2 measurements also were low in treated calves who did not have correspondingly high plasma 6-keto-PGF1 alpha concentration. Regional blood flow analysis did not reveal correlations between prostanoid concentrations and altered blood flow to selected tissues.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of surgical manipulation, placental fluid, and flunixin meglumine on fetal viability and prostaglandin F2 alpha release in the gravid uterus of mares

Twenty-one pregnant mares with single or twin conceptuses between 41 and 65 days of gestational age were allotted to 5 treatment groups. A ventral median celiotomy was performed in all mares. In group-1 mares (3 mares, single conceptus), the uterus and fetus were palpated for 5 minutes. In group-2 mares (3 mares, single conceptus, flunixin meglumine), 250 ml of sterile placental fluid was injected into the nongravid uterine horn. In group-3 mares (4 mares, unicornuate twin conceptuses), group-4 mares (3 mares, unicornuate twin conceptuses, flunixin meglumine), and group-5 mares (8 mares, bicornuate twin conceptuses, flunixin meglumine), 1 conceptus was removed from the uterus via hysterotomy. All mares received progesterone prophylactically until day 100 of gestation or until the fetus died. The 3 mares in group 1 delivered clinically normal, live foals. The mean prostaglandin F2 alpha metabolite (PGFM) plasma concentration peaked at 180 +/- 5.2 pg/ml during uterine manipulation and fetal palpation, then declined to baseline by 1 hour. Free placental fluid (group 2) undermined the chorioallantois ventrally and resulted in fetal death within 3 hours after surgery. The mean PGFM plasma concentration peaked at 39 +/- 4 pg/ml following injection of placental fluid. None of the remaining fetuses in the 7 mares with unicornuate twin conceptuses (groups 3 and 4) survived. Five mares with unicornuate twin conceptuses (group 5) delivered single viable foals. In another mare in group 5, the fetus was alive 4 days after surgery, when the mare was euthanatized for a fractured femur.(ABSTRACT TRUNCATED AT 250 WORDS)     

Clinical efficacy of diclofenac sodium and flunixin meglumine as adjuncts to antibacterial treatment of respiratory disease of calves

Objective To compare the efficacy of the non-steroidal antiinflammatory drugs, diclofenac sodium and flunixin meglumine as adjuncts to the antibiotic treatment of bovine respiratory disease (BRD). Procedure We randomly allocated 80 Holstein calves with BRD to three groups. All the calves received a dose of 2.5 mg/kg tulathromycin by single subcutaneous injection and two of the groups received, in addition, either 2.5 mg/kg diclofenac sodium as a single intramuscular injection (diclofenac group, n = 30) or 2.2 mg/kg flunixin meglumine as an intravenous injection on the first three consecutive days after tulathromycin administration (flunixin group, n = 30). All calves were given a clinical score prior to initial treatment (day 0) and after treatment (days 1, 2, 3, 7 and 14) by observing appetite, demeanour, rectal temperature, the rate and type of respiration, presence or absence of coughing, and nasal discharge. Results During the first 48 h, improvement of adverse signs of respiratory disease, such as pyrexia and elevated respiratory rate, and of a high clinical index score was significant in the two adjunct groups compared with the calves receiving antibiotic alone. The reduction in pyrexia was greatest in the diclofenac group. There were no statically significant differences between treatment groups with regard to eventual perceived recovery from respiratory disease in 14 days. Conclusion In this trial, a single intramuscular dose of diclofenac sodium was equally effective as three intravenous injections of flunixin meglumine given on consecutive days as adjunctive therapy for BRD.     

The efficacy of dexamethasone and flunixin meglumine in treating endotoxin-induced changes in calves

Eicosanoids have been implicated in the pathophysiology of endotoxic shock. Drugs which alter eicosanoid production such as corticosteroids and non-steroidal anti-inflammatory drugs (NSAID) are beneficial in treating endotoxic shock. Experiments were conducted to investigate the efficacy of dexamethasone, a corticosteroid, and/or flunixin meglumine, a NSAID, in treating endotoxin-induced changes in calves.Fourteen male calves were assigned to one of four treatment groups: group 1, endotoxin-untreated; group 2, endotoxin-flunixin meglumine treated; group 3, endotoxin-dexamethasone-treated; group 4, endotoxin-flunixin meglumine and dexamethasone-treated. Each calf was given three intravenous and intraperitoneal injections of E. coli endotoxin. Hemodynamic, blood gas, blood chemical and eicosanoid level determinations were obtained.Thirty minutes after endotoxin injection, pulmonary artery pressure (PAP) increased and cardiac output (CO) decreased compared with baseline, corresponding to increased thromboxaneB₂ levels in groups 1 and 3. These groups exhibited a decreased mean arterial pressure (MAP) at three and five hours corresponding to increased 6-keto-prostaglandinF_lalpha. The MAP, PAP and CO of group 4 remained near baseline for the entire six hours, except for a late drop in MAP. Lactic acid levels were significantly increased and arterial bicarbonate levels were reduced by six hours in all groups except for group 4. These results indicate that the combination treatment of flunixin meglumine and dexamethasone prevents many of the metabolic derangements observed during endotoxic shock in calves.     

Effect of preoperative administration of erythromycin or flunixin meglumine on postoperative abomasal emptying rate in dairy cows undergoing surgical correction of left displacement of the abomasum

Objective: To determine whether preoperative administration of erythromycin or flunixin meglumine altered postoperative abomasal emptying rate, rumen contraction rate, or milk production in dairy cattle undergoing surgical correction of left displacement of the abomasum (LDA). DESIGN: Nonrandomized, controlled clinical trial. ANIMALS: 45 lactating Holstein-Friesian cows with LDA. PROCEDURES: Cows were alternately assigned to an erythromycin (10 mg/kg [4.5 mg/lb], IM), flunixin (2.2 mg/kg [1.0 mg/lb], IV), or control group (n = 15/group). Treatments were administered once 1 hour before surgical correction of LDA. D-Xylose solution (50%; 0.5 g/kg [0.23 g/lb]) was injected into the abomasal lumen during surgery, and venous blood samples were periodically obtained to determine time to maximum serum D-xylose concentration. RESULTS: Abomasal emptying rate was significantly faster in cows treated with erythromycin (mean +/- SD time to maximum serum D-xylose concentration, 149 +/- 48 minutes) than in control cows (277 +/- 95 minutes) but was not significantly different between cows treated with flunixin (230 +/- 49 minutes) and control cows. Cows treated with erythromycin had significantly greater milk production, relative to production before surgery, on postoperative days 1 and 2 than did control cows. Cows in the erythromycin and flunixin groups had a significantly higher rumen contraction rate on the first postoperative day than did control cows. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that preoperative administration of a single dose of erythromycin increased abomasal emptying rate, rumen contraction rate, and milk production in the immediate postoperative period in cows undergoing surgical correction of LDA.     

A comparative study of the effects of meloxicam and flunixin meglumine (NSAIDs) as adjunctive therapy on interferon and tumor necrosis factor production in calves suffering from enzootic bronchopneumonia

The study was performed on 18 Black-and-White Lowland Breed calves with clinical signs of enzootic bronchopneumonia divided into three groups and respectively treated with oxytetracycline and meloxicam--Group I (9 animals); oxytetracycline and flunixin meglumine--Group II (3 animals); and oxytetracycline only--Group III (6 animals--control). The following observations were recorded before treatment (1st day) and two days later (3rd day): body temperature, the serum level of interferon (IFN) and tumor necrosis factor (TNF) as well as cytokine production by bronchoalveolar lavage (BAL) cells. The treatment of calves with a combination of oxytetracycline and meloxicam (Group I) and especially with oxytetracycline and flunixin meglumine (Group II) caused a significantly faster, in comparison to the control group, normalization of body temperature. Both drugs, meloxicam and especially flunixin meglumine, inhibited excessive TNF production in the organism (measured as the serum level of cytokine). Moreover, BAL cells isolated from calves treated with both NSAIDs were still able, ex vivo, to release TNF, in contrast to the control group (treated only with tetracycline) which lost the ability to produce TNF. The treatment of the calves with meloxicam and flunixin meglumine did not significantly influence the levels of IFN in sera but normalized ex vivo IFN production in BAL cells. These results suggest that the combination of meloxicam with an antibiotic or flunixin meglumine with an antibiotic which does not exert an immunosuppressive influence on the organism of calves suffering from enzootic bronchopneumonia is equally effective in the treatment of calves and superior to the antibiotic alone.     

Effect of flunixin meglumine on surgical wound strength and healing in the rat

Forty male adolescent Sprague-Dawley rats were anesthetized and standardized ventral midline laparotomies and uniform-length gastrotomies and typhlotomies were performed. The visceral and abdominal surgically inflicted wounds were closed with 5-0 polypropylene and 4-0 nylon suture, respectively. The rats were allotted into 4 groups (10 rats/group); 2 groups were not given flunixin meglumine (controls) and 2 groups were given flunixin meglumine (1.1 mg/kg of body weight, IM, every 12 hours). On day 5 and again on day 14 after surgery, 1 control and 1 flunixin meglumine-treated group were euthanatized. Tensile strength of the skin and linea alba incisions was determined, using a computerized tensiometer. Gastric and cecal incision bursting strengths were determined, using a pressure manometer. Flunixin meglumine significantly (P less than 0.05) decreased the tensile strength of wounds in the skin and linea alba, but did not affect visceral bursting strength at day 5 after surgery. At day 14 after surgery, a significant difference in wound strength was not found between the flunixin meglumine and control groups in any of the tissues evaluated. Flunixin meglumine had an adverse influence on the inflammatory stage of wound repair, but not on the proliferative stage, when fibroplasia is a major factor in wound strength. Major histologic differences were not found in the incision wounds of flunixin meglumine-treated and nontreated control rats.     

Clinical efficacy of meloxicam (Metacam) and flunixin (Finadyne) as adjuncts to antibacterial treatment of respiratory disease in fattening cattle

The clinical efficacy of two non-steroidal anti-inflammatory drugs (NSAIDs), meloxicam (Metacam 20 mg/ml) and flunixin meglumine (Finadyne), as adjuncts to antibacterial therapy in the treatment of acute febrile respiratory disease in cattle was compared. The randomised blind, positive controlled study was conducted under feedlot conditions in Mexico. Overall, 201 female cattle (weighing 220-250 kg) diagnosed with bronchopneumonia at the feedlot were recruited into the study. On Day 0 all animals were treated with 20 mg oxytetracycline/kg body-weight (Bivatop 200) by subcutaneous injection, in conjunction with either meloxicam (0.5 mg/kg subcutaneously, Metacam 20 mg/ml, n = 100), or flunixin meglumine (2.2 mg/kg intravenously, Finadyne, n = 101). According to label instructions, meloxicam was administered as a single dose, whereas flunixin meglumine could be administered daily for up to 3 consecutive days depending on the rectal temperature (with re-administration, if rectal temperature > or = 40.0 degrees C). Rectal temperature, respiratory rate, appetite, dyspnoea, coughing, nasal discharge and general condition were recorded on Days 0 (prior to treatment), 1, 2, 3 and 7 using a weighted numerical score. Scores were summed to generate a 'Clinical Sum Score' (CSS, range 7 to 24 points). Individual animal body weights were measured on Days 0 and 7. Nasal swabs were collected from 10 animals per treatment group on Day 0 for microbiological culture. Clinical parameters and the mean CSS showed no significant differences between treatment groups with mean CSS on Days 0 and 7 of 16.18 and 10.55 in the meloxicam group and 16.41 and 10.88 in the flunixin meglumine group. However, a significantly lower mean rectal temperature was measured in the meloxicam group on Day 2 (p < or = 0.01). No significant differences in mean body weights were found between groups. Repeated administration of flunixin meglumine was performed in 45% of the animals. No suspected adverse drug events related to treatments were reported. It is concluded that a single subcutaneous dose of meloxicam was as clinically effective as up to 3 consecutive daily intravenous doses of flunixin meglumine when used as an adjunctive therapy to antibacterial therapy in the treatment of acute febrile respiratory disease in feedlot cattle.     

Effects of flunixin meglumine on endotoxin-induced prostaglandin F2 alpha secretion during early pregnancy in mares

The role of prostaglandin F2 alpha (PGF2 alpha) in embryonic loss following induced endotoxemia was studied in mares that were 21 to 44 days pregnant. Thirteen pregnant mares were treated with a nonsteroidal anti-inflammatory drug, flunixin meglumine, to inhibit the synthesis of PGF2 alpha caused by Salmonella typhimurium endotoxin given IV. Flunixin meglumine was administered either before injection of the endotoxin (group 1, -10 min; n = 7), or after endotoxin injection into the mares (group 2, 1 hour, n = 3; group 3, 2 hours, n = 3); 12 pregnant mares (group 4) were given only S typhimurium endotoxin. In group 4, the secretion of PGF2 alpha, as determined by plasma 15-keto-13,14-dihydro-PGF2 alpha concentrations, was biphasic, initially peaking at 30 minutes followed by a second, larger peak approximately 105 minutes after the endotoxin was given IV. When flunixin meglumine was administered at -10 minutes, synthesis of PGF2 alpha was inhibited for several hours, after administration of flunixin meglumine at 1 hour, the second secretory surge of PGF2 alpha was blocked, and administration of the drug at 2 hours did not substantially modify the secretion of PGF2 alpha. Plasma progesterone concentrations were unchanged after endotoxin injections were given in group 1. In group 2, progesterone values decreased less than 2 ng/ml and remained low for several days. In group 3 and group 4, progesterone concentrations decreased to values less than 0.5 ng/ml by 48 hours after endotoxin injections were given.(ABSTRACT TRUNCATED AT 250 WORDS)     

The behavioral assessment and alleviation of pain associated with castration in beef calves treated with flunixin meglumine and caudal lidocaine epidural anesthesia with epinephrine

The objectives of this study were 1) to determine the effects of flunixin megulmine in combination with caudal epidural anesthesia as a postoperative analgesic in beef calves following surgical castration, and 2) to consider stride length and pedometry as potential behavioral assessment tools for detecting postcastration pain. Surgical castration was performed in 101 beef calves randomly assigned to 3 treatment subgroups: 1) castration without anesthesia (SURG); 2) castration following lidocaine with epinephrine caudal epidural anesthesia (SURG + EPI); 3) castration following lidocaine with epinephrine caudal epidural anesthesia and flunixin meglumine (SURG + EPI + F). Several outcomes, including pedometer counts, changes in stride length, subjective visual assessment of pain, instantaneous scan sampling of the calves’ postoperative activities, and the amount of movement and vocalization during the castration procedure, were measured to identify and quantify pain. The results indicated that stride length and the number of steps taken by calves after castration appear to be good measures of pain. Significant differences found between treatment groups for stride length and visual assessments suggest that flunixin meglumine can be considered to provide visible pain relief up to 8 hours postcastration.     

Effect of age and training status on pharmacokinetics of flunixin meglumine in thoroughbreds

The effect of age and training status on the pharmacokinetics of flunixin meglumine was evaluated in 16 Thoroughbreds. Horses were assigned to 1 of 3 groups on the basis of age and training status: group A (n = 6), horses in active training and less than or equal to 5 years old; group B (n = 5), horses out of training for a minimum of 6 weeks and less than or equal to 5 years old; and group C (n = 5), horses out of training for at least 2 years and greater than or equal to 9 years old. After administration of 500 mg of flunixin meglumine IV, multiple serum and urine samples were obtained over 24 hours and assayed for flunixin by high-performance liquid chromatography. Although the mean distribution rate constant and volume of distribution were similar for the 3 groups, mean total body clearance and elimination rate constant were significantly (P less than 0.05) greater and half-life significantly (P less than 0.01) less in groups A and B, compared with group C. Differences in pharmacokinetic values were not observed between the horses in group A and B. In addition, the changes in clearance, elimination rate constant, and half-life of flunixin were found to significantly (P less than 0.05) correlate with age. The results of this investigation indicated that age, but not training status, influences disposition of flunixin meglumine in Thoroughbreds.     

Pharmacokinetics of flunixin in mature heifers following multiple intravenous administration

The pharmacokinetics of flunixin meglumine was determined after its multiple (altogether 4 doses at 24-hours intervals) intravenous administration at a dose of 2.2 mg/kg body weight in six mature clinically healthy heifers. Plasma flunixin and its metabolite 5-hydroxyflunixin concentrations were analyzed with high-pressure liquid chromatography using an assay with a lower limit detection of 0.03 microg/ml for both substances. Plasma concentrations versus time curves were described by a two compartment open model. Mean plasma flunixin concentrations were similar on day 1 and 4, and than rapidly decreased (within 2 hours) from initial concentrations higher than 10 microg/ml to the concentrations lower than 1 microg/ml. The distribution phase of flunixin was short (t0.5 alpha = 0.29 +/- 0.16 and 0.18 +/- 0.04 on day 1 and 4, respectively) and the elimination phase was more prolonged (t0.5 beta = 3.30 +/- 0.60 and 3.26 +/- 0.22 on day 1 and 4, respectively). The mean residence time of flunixin was similar on day 1 (1.83 +/- 0.83) and 4 (1.88 +/- 0.46), and for 5-hydroxyflunixin this parameter was insignificantly (P > 0.05) higher on day 1 (5.49 +/- 2.22) as compared to that found on day 4 (3.99 +/- 2.17). The clearance of flunixin was similar on both examined days (0.23 +/- 0.12 on day 1 and 0.31 +/- 0.15 on day 4), and for 5-hydroxyflunixin was insignificantly (P > 0.05) lower on day 1 (2.37 +/- 1.21) as compared to that determined on day 4 (3.23 +/- 1.06). Our data indicate that multiple administration of flunixin did not alter significantly the parent drug and its metabolite concentrations in plasma, however may cause some small changes in pharmacokinetic parameters.     

Effects of ivermectin and fenbendazole in strategic treatment of gastrointestinal nematode infections in cattle

Four groups of 18 beef calves each were used to evaluate effects of different treatments on parasite control and weight gains. The investigation extended from November 1986 (weaning) to October 1987. Group-1 calves were treated with ivermectin (200 micrograms/kg of body weight, SC) at approximately 6-week intervals for a total of 8 treatments; group-2 calves were given the same dosage of ivermectin by the same route of administration as group-1 calves in November, March, and July; group-3 calves were given fenbendazole paste (5 mg/kg, PO) at the same times as group-2 calves; and group-4 calves served as untreated controls with provision for ivermectin salvage treatment. All groups grazed on individual pairs of larval-contaminated, 1.6-ha pastures. Highest (P less than 0.05) initial worm counts in fall tracer calves were found in group 3 (Ostertagia ostertagi and Trichostrongylus axei adults) and group 4 (O ostertagi and Haemonchus adults). Fecal egg counts of group-1 calves were low throughout the experiment and pasture larval counts remained negligible after July. Egg counts and larval counts of other groups remained higher into summer. Worm counts, including O ostertagi inhibited early fourth-stage larvae (EL4), were highest (P less than 0.05) in groups-3 and -4 spring tracer calves; numbers of O ostertagi EL4 were similarly high in groups 2, 3, and 4; and T axei counts were highest (P less than 0.05) in groups-3 and -4 yearlings slaughtered in spring. Liveweights of group-1 calves were greater (P less than 0.05) than in other groups from March 2 to October, and by July 2, group-2 calves had a liveweight advantage over group-4 calves. Group-3 calves had the lowest rate of gain from March to July and mean liveweight of the group was less (P less than 0.05) than in all other groups from April to October. Only minimal worm numbers were recovered from groups-1 or -2 calves in October. Large numbers of O ostertagi and T axei were recovered from group-4 calves and O ostertagi from group-3 calves. A few calves in groups 3 and 4, but particularly in group 4, were affected by type-II disease (chronic to acute gastritis caused by maturation and emergence of previously inhibited larvae) from August to October. Final mean liveweights in descending order were 365 kg in group 1, 328 kg in group 2, 316 kg in group 4, and 281 kg in group 3.     

Pharmacokinetics of flunixin meglumine in lactating cattle after single and multiple intramuscular and intravenous administrations

The pharmacokinetics of flunixin were studied in 6 adult lactating cattle after administration of single IV and IM doses at 1.1 mg/kg of body weight. A crossover design was used, with route of first administration in each cow determined randomly. Plasma and milk concentrations of total flunixin were determined by use of high-pressure liquid chromatography, using an assay with a lower limit of detection of 50 ng of flunixin/ml. The pharmacokinetics of flunixin were best described by a 2-compartment, open model. After IV administration, mean plasma flunixin concentrations rapidly decreased from initial concentrations of greater than 10 micrograms/ml to nondetectable concentrations at 12 hours after administration. The distribution phase was short (t1/2 alpha, harmonic mean = 0.16 hours) and the elimination phase was more prolonged (t1/2 beta, harmonic mean = 3.14 hours). Mean +/- SD clearance after IV administration was 2.51 +/- 0.96 ml/kg/min. After IM administration, the harmonic mean for the elimination phase (t1/2 beta) was prolonged at 5.20 hours. Bioavailability after IM dosing gave a mean +/- SD (n = 5) of 76.0 +/- 28.0%. Adult, lactating cows (n = 6) were challenge inoculated with endotoxin as a model of acute coliform mastitis. After multiple administration (total of 7 doses; first IV, remainder IM) of 1.1 mg/kg doses of flunixin at 8-hour intervals, plasma flunixin concentrations were approximately 1 microgram/ml at 2 hours after each dosing and 0.5 micrograms/ml just prior to each dosing. Flunixin was not detected in milk at any sampling during the study.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of ivermectin on control of gastrointestinal nematodes and weight gain in weaner-yearling beef cattle

Four groups of 16 crossbred beef calves were used in evaluating different anthelmintic treatment schedules: group 1 was given ivermectin (IVM) at weaning only (October 31) and grazed on initially safe pasture; group 2 was given IVM at weaning, on January 28, and on April 22, and grazed on contaminated pasture; and group 3 was given IVM at weaning and on April 22, and grazed on contaminated pasture; and group-4 was group treated with fenbendazole (FBZ) at weaning only, with provision for individual salvage treatment, and grazed on contaminated pasture. The investigation was from Oct 31, 1984, to Oct 9, 1985. Initially high fecal egg counts at weaning were more effectively reduced by IVM than by FBZ, and the effect of safe pasture was evident in minimal worm burdens in tracer calves grazed with group-1 cattle during November and least amount of weight loss in group-1 yearlings during winter. Fecal egg counts, pasture larval counts, and plasma pepsinogen concentrations remained low in group 2 after the January treatment. Fecal egg counts of the other groups increased substantially during late winter and spring, but pasture larval counts increased only on group-1 and group-4 pastures. During spring, highest worm burdens were found in group-1 and group-4 tracer calves (grazed in April) and in group-3 and group-4 yearlings (slaughtered in early April). Six cattle of group 4 were salvage treated with FBZ in February and April. Greatest gains were observed from March through June, with group-2 and group-1 cattle gaining the most.(ABSTRACT TRUNCATED AT 250 WORDS)     

Distribution of flunixin meglumine and firocoxib into aqueous humor of horses

Background: Nonsteroidal anti‐inflammatory drugs (NSAIDs) are commonly used systemically for the treatment of inflammatory ocular disease in horses. However, little information exists regarding the ocular penetration of this class of drugs in the horse. Objective: To determine the distribution of orally administered flunixin meglumine and firocoxib into the aqueous humor of horses. Animals: Fifteen healthy adult horses with no evidence of ophthalmic disease. Methods: Horses were randomly assigned to a control group and 2 treatment groups of equal sizes (n = 5). Horses assigned to the treatment groups received an NSAID (flunixin meglumine, 1.1 mg/kg PO q24h or firocoxib, 0.1 mg/kg PO q24h for 7 days). Horses in the control group received no medications. Concentrations of flunixin meglumine and firocoxib in serum and aqueous humor and prostaglandin (PG) E₂ in aqueous humor were determined on days 1, 3, and 5 and aqueous : serum ratios were calculated. Results: Firocoxib penetrated the aqueous humor to a significantly greater extent than did flunixin meglumine at days 3 and 5. Aqueous : serum ratios were 3.59 ± 3.32 and 11.99 ± 4.62% for flunixin meglumine and firocoxib, respectively. Ocular PGE₂ concentrations showed no differences at any time point among study groups. Conclusions and Clinical Importance: Both flunixin meglumine and firocoxib penetrated into the aqueous humor of horses. This study suggests that orally administered firocoxib penetrates the aqueous humor better than orally administered flunixin meglumine at label dosages in the absence of ocular inflammation. Firocoxib should be considered for the treatment of inflammatory ophthalmic lesions in horses at risk for the development of adverse effects associated with nonselective NSAID administration.     

Endotoxin-induced hemodynamic changes in dogs: role of thromboxane and prostaglandin I2

Plasma concentrations of thromboxane and prostaglandin I2 (PGI2) before and after IV injection of endotoxin and resulting hemodynamic changes were evaluated. Effects of flunixin meglumine on plasma concentrations of these prostaglandins and the related hemodynamic changes were also determined. Shock was induced in 2 groups of anesthetized dogs. Four dogs were given endotoxin only and 4 dogs were given endotoxin and then were treated with flunixin meglumine. Arterial blood pressure (BP), cardiac output (CO), and heart rate were measured, and blood samples were collected at postendotoxin hours (PEH) 0, 0.1, 0.25, 0.5, 1, 2, 3, and 4. Plasma thromboxane and PGI2 concentrations were increased in canine endotoxic shock. Thromboxane concentration was highest early in shock, and appeared to be associated with an initial decrease in BP and CO. The increased concentration of PGI2 was associated with systemic hypotension at PEH 1 to 2. Treatment of dogs with flunixin meglumine at PEH 0.07 prevented further increase of thromboxane and blocked the release of PGI2, resulting in an increased CO, BP, and tissue aerobic metabolism.