Development of a guar gum film with lysine clonixinate for periodontal treatments.

Periodontal pain is a public health problem derived from different conditions, including periodontal diseases, prosthetic complications, and even extractions performed by dentist. There are various treatments to control acute dental pain, being the administration of analgesics, such as Lysine Clonixinate (LC), a common practice. Unfortunately, higher and repeated dosages are usually required. The purpose of this work was to develop a prolonged release pharmaceutical form as an alternative treatment for dental pain. Hence, we conceived a film based on guar gum and loaded different concentrations of LC. We evaluated the film's appearance, brittleness, strength, and flexibility, and then chose one formulation for adequate characteristics. Subsequently, we assessed the morphology, thermal behavior, and swelling properties of the films (LC-free and -loaded). Finally, we performed the release studies of LC from the films in vitro using a simulated saliva medium and employed several mathematical models to evaluate the release kinetics. Guar gum is a natural polymer obtained from the endosperm of Cyamopsis tetragonolobus that presents properties such as biosafety, biocompatibility, and biodegradability. Thus, it represents a potential excipient for use in pharmaceutical formulations. Moreover, our results revealed that the LC-loaded film presented a high adherence, suitable swelling behavior, high LC content, and a prolonged drug release. Therefore, the LC-loaded film may be considered a potential option to be applied as an alternative to treat dental pain.

Randomized controlled trial comparison of analgesic drugs for control of pain associated with induced lameness in lactating dairy cattle.

Both the economic loss and welfare implications of lameness affect the dairy industry. Currently no analgesic drugs are approved to alleviate lameness-associated pain in lactating dairy cattle in the United States. In this randomized controlled trial, 48 lactating Holsteins were enrolled to evaluate the effect of oral meloxicam and i.v. flunixin meglumine on induced lameness. Cows were allocated to 1 of 4 treatment groups (n = 12 per group): lameness and flunixin meglumine (LAME + FLU); lameness and meloxicam (LAME + MEL); lameness and placebo (LAME + PLBO); or sham induction and placebo (SHAM + PLBO). Six hours before treatment, arthritis-synovitis was induced in the distal interphalangeal joint with 20 mg of amphotericin B, whereas SHAM cows were given an intra-articular injection of an equal volume (4 mL) of isotonic saline. Cows in LAME + FLU received 2.2 mg/kg flunixin meglumine i.v. and whey protein placebo orally; LAME + MEL were administered 1 mg/kg meloxicam orally and 2 mL/45 kg sterile saline placebo i.v.; LAME + PLBO were administered 2 mL/45 kg sterile saline placebo i.v. and whey protein placebo orally; and SHAM + PLBO received 2 mL/45 kg sterile saline placebo i.v. and whey protein placebo orally. The initial treatment of MEL, FLU, or PLBO was identified as time 0 h and followed by a second dose 24 h later with data collection for 120 h. The methods used to assess analgesic efficacy were electronic pressure mat, visual lameness assessment, visual analog score, plasma cortisol concentration, plasma substance P concentration, mechanical nociception threshold, and infrared thermography imaging. Linear mixed effect modeling was the primary method of statistical analysis. Visual lameness scoring indicated a lower proportion of the FLU + LAME group was lame at the T2 h and T8 h time points in comparison to the positive controls, whereas MEL therapy resulted in a lower proportion of lame cows at the T8 h time point. Cortisol area under the effect curve was lower following FLU therapy compared with LAME + PBLO for the 0-2 h (LSM difference = 35.1 ng·h/mL, 95% CI: 6.8, 63.3 ng·h/mL), 2-8 h (LSM difference = 120.6 ng·h/mL, 95% CI: 77.2, 164.0 ng·h/mL), and 0-24 h (LSM difference = 226.0 ng·h/mL, 95% CI: 103.3, 348.8 ng·h/mL) time intervals. Following MEL therapy, cortisol area under the effect curve was lower than LAME + PLBO for both the 2 to 8 h (LSM difference = 93.6 ng·h/mL, 95% CI: 50.2, 137.0 ng·h/mL) and 0 to 24 h time intervals (LSM difference = 187.6 ng·h/mL, 95% CI: 64.9, 310.4 ng·h/mL). Analysis of data from other assessment modalities failed to discern biologically relevant differences between treatment groups. We conclude that meaningful differences were evident for visual lameness assessment and cortisol from MEL and FLU treatment versus the positive control. Further clinical research is needed toward development of a model that will create reproducible events that are more pronounced in severity and duration of lameness which can be validated as a substitute for naturally occurring lameness cases.

Effects of various mastitis treatments on the reproductive performance of cows.

BACKGROUND: The purpose of the study described here was to evaluate the effects of different supportive treatments - such as antioxidants, immunomodulators, and nonsteroidal anti-inflammatory drugs (NSAIDs) - in mastitic cows treated with intramammary antibiotics on the efficacy of mastitis therapy and fertility indices. Fertility indices, including time to first insemination, conception rate, time between calving and conception (open days), and number of services per conception (insemination index), were evaluated for 300 dairy cows. Sixty cows without apparent clinical signs of mastitis were assigned 100 days after calving to a Control group. Another 240 cows with clinical mastitis were systematically divided into four experimental groups (I-IV) of 60 cows each. All mastitic cows were treated with approved intramammary antibiotics in recommended doses. Cows in Group I were treated with intramammary antibiotics only. Cows in Groups II, III, and IV, received intramammary antibiotic therapy and a single injection with antioxidants, an immunomodulator (lysozyme dimer), or an NSAID (flunixin meglumine), respectively. RESULTS: The lowest treatment efficacy of mastitic quarters and cows was noted in Group I (51.6 and 53.3%; p > 0.05). The best recovery rate was noted in Group II (63.3 and 66.7%; p > 0.05), followed by Group III (58.3 and 60.9%) and Group IV (58.3 and 58.0%; p > 0.05). The above data did not differ statistically (p > 0.05). The animals with mastitis (Groups I-IV) showed prolonged time to first insemination, more open days, higher insemination index, and lower conception rate than the control cows (p <  0.05). The conception rate of healthy cows and of successfully treated cows was insignificantly lower than that of cows required prolonged antibiotic therapy. Supportive treatments improved the mastitis recovery rate compared with intramammary antibiotics only. The efficacy of mastitis treatments affected the reproduction indices: in cows requiring prolonged treatment with antioxidants, a shorter time to first insemination was needed than in other groups (p <  0.05). Fewer days open were observed between the group with antioxidants and the control group (p <  0.05). CONCLUSIONS: Clinical mastitis negatively affects reproductive indices (days open, pregnancy rate after first AI, NSC) in dairy cows. Different types of supportive medicine, such as antioxidants (vitamin C and E, and ß-carotene), lysozyme dimer, or NSAID can be useful in improving fertility in mastitis cows treated with antibiotic only. It has been proven that each supportive treatment improved antibiotics efficiency and the antibiotic combined with the antioxidants was the most effective treatment.

Preliminary study on the effects of enrofloxacin, flunixin meglumine and pegbovigrastim on Mycoplasma bovis pneumonia.

BACKGROUND: Mycoplasma bovis is a causative agent of disease in cattle causing many clinical conditions. Currently there are no commercial M. bovis vaccines in Europe and treatment is difficult with decreased antimicrobial susceptibility of M. bovis field isolates. Using an M. bovis calf infection model the effectiveness of enrofloxacin given alone; in combination with flunixin meglumine, a nonsteroidal anti-inflammatory drug; and a group with an additional treatment of pegbovigrastim, an immunostimulator, was evaluated. RESULTS: Enrofloxacin given alone stimulated a strong immune response, reduced the clinical manifestation and lung lessions of the M. bovis infection. In contrast the combination therapy appeared ineffective. CONCLUSIONS: In this experiment enrofloxacin given alone appeared to be the most effective treatment of the M. bovis affected calves, whereas co-administration with flunixin meglumine, and pegbovigrastim was not beneficial in this trial.

The impact of pain on the pharmacokinetics of transdermal flunixin meglumine administered at the time of cautery dehorning in Holstein calves.

OBJECTIVE: To study the influence of pain on the pharmacokinetics and anti-inflammatory actions of transdermal flunixin administered at dehorning. STUDY DESIGN: Prospective, crossover, clinical study. ANIMALS: A total of 16 male Holstein calves, aged 6-8 weeks weighing 61.3 ± 6.6 kg. METHODS: Calves were randomly assigned to one of two treatments: transdermal flunixin and dehorning (PAIN) or transdermal flunixin and sham dehorning (NO PAIN). Flunixin meglumine (3.33 mg kg-1) was administered topically as a pour-on concurrently with hot iron dehorning or sham dehorning. The calves were subjected to the alternative treatment 14 days later. Blood samples were collected at predetermined time points up to 72 hours for measurement of plasma flunixin concentrations. Pharmacokinetics parameters were determined using noncompartmental analysis. Prostaglandin E2 (PGE2) concentration was determined using a commercial enzyme-linked immunosorbent assay. The 80% inhibition concentration (IC80) of PGE2 was determined using nonlinear regression. Pharmacokinetic data were statistically analyzed using paired t tests and Wilcoxon rank sums for nonparametric data. Flunixin and PGE2 concentrations were log transformed and analyzed using repeated measures. RESULTS: A total of 15 calves completed the study. Plasma half-life of flunixin was significantly longer in PAIN (10.09 hours) than NO PAIN (7.16 hours) (p = 0.0202). Bioavailability of transdermal flunixin was 30% and 37% in PAIN and NO PAIN, respectively (p = 0.097). Maximum plasma concentrations of flunixin were 0.95 and 1.16 µg mL-1 in PAIN and NO PAIN, respectively (p = 0.089). However, there was a treatment (PAIN versus NO PAIN) by time interaction (p = 0.0353). PGE2 concentrations were significantly lower in the PAIN treatment at 48 and 72 hours (p = 0.0092 and p = 0.0287, respectively). The IC80 of PGE2 by flunixin was similar in both treatments (p = 0.88). CONCLUSION AND CLINICAL RELEVANCE: Pain alters the pharmacokinetics and anti-inflammatory effects of transdermally administered flunixin.

Short communication: Behavioral evaluation of the analgesic effect of flunixin meglumine in lame dairy cows.

The objective of this study was to evaluate the effect of flunixin meglumine treatment on lameness pain in dairy cows. Twenty-four lactating Holstein cows were enrolled in the study based on visual observation of abnormal locomotion. The primary measurement endpoint was weight-shifting between the rear limbs. Weight-shifting was calculated as the standard deviation of the weight borne on the rear limbs over a 15 min period; this value correlates directly with lameness pain in dairy cows. After collecting baseline weight-bearing data, we randomly assigned cows to 1 of 2 treatment groups: 2.2 mg/kg body weight flunixin meglumine (2 mL/45 kg) or an equivalent volume of isotonic sterile saline solution. Weight-bearing data were collected from each cow at 2, 6, 12, and 24 h after a single intravenous drug treatment. Mean locomotion scores over the 2 d before treatment were 2.38/5 in the flunixin-treated group and 2.43/5 in the saline-treated control group; these values were not significantly different. Weight-shifting values were also not significantly different on either pretreatment day. Cows treated with flunixin meglumine showed significantly less weight-shifting between the rear limbs at 6, 12, and 24 h after treatment compared with saline-treated controls, providing evidence that flunixin meglumine alleviates lameness-associated pain.

Comparative therapeutic effect of steroidal and non-steroidal anti-inflammatory drugs on pro-inflammatory cytokine production in water buffalo calves (Bubalus bubalis) naturally infected with bronchopneumonia: a randomized clinical trial.

In the current study, we compared the therapeutic effects of a non-steroidal and a steroidal anti-inflammatory drug on the production of pro-inflammatory cytokines, interleukin-1ß (IL-1ß), interleukin-6 (IL-6), interleukin-12p40 (IL-12p40), interferon gamma (IFNγ), and tumor necrosis factor alpha (TNF-α) in the blood of water buffalo (Bubalus bubalis) calves naturally infected by bronchopneumonia. Twenty-seven buffalo calves (7 ± 2-month-old, 163 ± 12 kg) reared in smallholder farms in El-Dakahlia province in Egypt were identified to have bronchopneumonia and randomly allocated into three equal groups. Ten clinically healthy buffalo calves with negative bronchoalveolar lavage results were served as negative control. Diseased calves were treated with tulathromycin alone, a combination of tulathromycin with dexamethasone (steroidal anti-inflammatory drug) or tulathromycin with flunixin meglumine (non-steroidal anti-inflammatory drug). The results revealed significant elevations (P < 0.05) in the production of selected cytokines in all diseased calves in comparison with healthy animals. Six days post-treatment, a significant inhibition (P < 0.05) in the production of all assessed cytokines was observed in the blood of all treated calves. Interestingly, the serum concentrations of IL-1ß and IL-12p40 were returned to the normal levels in pneumonic calves treated with the combination therapy of tulathromycin and flunixin meglumine. A strong significant positive correlation (P < 0.05) was detected between clinical sum scoring and IL-12p40 and TNF-α concentrations. The obtained results indicate the selectively potent anti-inflammatory effect of flunixin meglumine on the production of pro-inflammatory cytokines in pneumonic buffalo calves and highlight the efficacy of flunixin meglumine in the treatment of bronchopneumonia in buffalo calves when used in combination with tulathromycin.

Therapeutic Use of Regional Limb Perfusion in a Chicken.

A 2-year-old, 3.8-kg male Rhode Island red rooster was examined for lameness and progressive swelling of the right foot of several month's duration. Radiographs of the right foot demonstrated soft tissue swelling and a smoothly marginated periosteal reaction evident of inflammation affecting the bones. Results of a complete blood count showed a moderate leukocytosis and an elevated total protein concentration. Systemic antibiotic and anti-inflammatory therapy was started, but the bird had not improved at recheck examination. After intravenous catheterization of the medial metatarsal vein and placing a tourniquet at the femoral-tibiotarsal joint of the right leg, regional limb perfusion with amikacin and flunixin meglumine was performed. Dimensions of both feet were measured with digital calipers, and surface temperatures of the feet were measured with an infrared thermometer. The rooster had improved activity level with decrease in lameness and measurable decrease in swelling of the right foot. Regional limb perfusion with intravenous antibiotics and nonsteroidal anti-inflammatory drugs is a viable treatment modality in avian species for suspected distal limb infection and cellulitis. This technique has potential valuable implications for a variety of avian species. Fluid support should be provided if using nephrotoxic drugs.

[Interleukin-2 for the treatment of cows with malignant catarrhal fever]. / Behandlung von Rindern mit Bösartigem Katarrhalfieber mit Interleukin-2.

The goal of this study was to investigate whether administration of interleukin-2 (IL-2) would improve the outcome of cows with malignant catarrhal fever (MCF). The study population consisted of ten healthy control cows and 22 cows with MCF. Nineteen cows with MCF and all of the controls were treated with either 2'500 U IL-2 or 25'000 U IL-2, administered intravenously. Three cows with MCF were not treated with IL-2 (MCF controls). All of the cows with MCF received danofloxacin, flunixin meglumine and intravenous fluid therapy. Blood samples for haematological and biochemical evaluation were collected once daily for six days in all cows. Of the 19 cows treated with IL-2, 13 were eutha nized because of deterioration. All cows with MCF that did not receive IL-2 died. The clinical condition of six cows treated with 2'500 U IL-2 gradually improved. Sur viving cows had significantly higher total leukocyte counts than cows that died or were euthanized. The main reason for leukopenia in non-surviving vs. surviv ing cows was persistent lymphopenia. Use of the lower IL-2 dose was associated with clinical recovery in some cows and this treatment might therefore be considered in valuable cows, provided that the lymphocyte count is within the reference interval.

Comparison of flunixin meglumine and meloxicam influence on postoperative and oxidative stress in ovariohysterectomized bitches.

The aim of this study was to compare the effect of flunixin meglumine (FM) and meloxicam (M) on postoperative and oxidative stress in ovariohysterectomized bitches. Twenty four bitches were divided into three groups (n = 8 in each) and treated during premedication as follows: FM (2.2 mg/kg, iv, Fluvil, Vilsan, Turkey), M (0.2 mg/kg, sc, Maxicam, Sanovel, Turkey) or 0.9% saline (1 ml, iv, IE, Turkey)--control (C) group. The concentrations of serum cortisol, nitric oxide (NO), malondialdehyde (MDA), antioxidant potential (AOP) and glutation (GSH) were measured in blood samples collected during incision (0 h), closure of incision line (0.5 h) and 1, 2.5, 12 and 24 hours after incision. It was observed that cortisol level was higher at 0.5, 1 and 2.5 h in group C (p < 0.05), 0.5 h in group FM (p < 0.001), and 1 and 2.5 h in group M (p < 0.01), as compared to that determine at 0 h. Group C showed higher cortisol level during 0.5 h (p < 0.05) than that found in the other groups. Group FM displayed lower levels during 1 h (p < 0.01) and 2.5 h (p < 0.05) as compared to those observed in other groups. Concentrations of MDA, AOP and GSH between all the groups did not show any significant differences. MDA level was higher at 0.5 and 1 h in group M (p < 0.05) than that found in group C and it was the lowest at 2.5 h in group C (p < 0.05). AOP was higher at 2.5 h in group FM and M (p < 0.05) than that observed in group C, and at 12 and 24 h in group M than that found in group C and FM. GSH did not show any significant differences between the groups. NO level in group FM after 12 h was higher (p < 0.05) than that at 0.5, 1 and 24 h. Moreover, NO level was lower at 0.5 (p < 0.01), 1 (p < 0.05) and 24 h (p < 0.05) in group FM than that observed in group C and M. In conclusion, flunixin meglumine decreases cortisol and NO levels more efficiently than meloxicam. Therefore, it is suggested that postoperative stress following ovariohysterectomy may be prevented by flunixin meglumine in bitches.

Prostaglandin E2 is an unreliable biomarker for inflammation in castrated piglets: a randomized controlled trial assessing pharmaceutical drug efficiency.

OBJECTIVE: To investigate the effect of intranasal (IN) flunixin meglumine (FM) and intra-inguinal (IG) lidocaine on castration inflammation using prostaglandin E2 (PGE2) concentration as a biomarker. METHODS: This randomized controlled trial was conducted in March 2022. Blood was collected at -24, 1, and 24 hours postcastration for PGE2 quantification from 195 piglets that received 1 of 8 treatments: (1) saline (1.5 mL) applied IG and IN (0.2 mL) followed by surgical castration (n = 24); (2) saline (1.5 mL) IG and IN (0.2 mL) followed by sham castration (25); (3) lidocaine (20 mg/kg or 1.5 mL) IG followed by surgical castration (24); (4) lidocaine (20 mg/kg or 1.5 mL) IG followed by sham castration (25); (5) FM (2.2 mg/kg) IN followed by surgical castration (25); (6) FM (2.2 mg/kg) IN followed by sham castration (24); (7) lidocaine (20 mg/kg or 1.5 mL) IG and FM (2.2 mg/kg) IN followed by surgical castration (24); and (8) lidocaine (20 mg/kg or 1.5 mL) IG and FM (2.2 mg/kg) IN followed by sham castration (24). RESULTS: Prostaglandin E2 concentrations did not increase following the castration procedure and were not an effective biomarker of castration inflammation. Piglets that received lidocaine demonstrated no difference in PGE2 levels across all time points. Piglets administered FM had lower PGE2 concentrations at 1 hour and 20 minutes postdrug administration in both the sham and castrated piglets. CONCLUSIONS: Prostaglandin E2 was not an effective biomarker to quantify castration inflammation. Flunixin meglumine was able to reduce PGE2 concentration in piglets regardless of castration procedure, but lidocaine had no impact. Decreased PGE2 levels in FM-treated pigs are likely associated with the drug's ability to mitigate a noncastration-associated inflammatory process occurring independent of the castration procedure. CLINICAL RELEVANCE: Flunixin meglumine reduced circulating PGE2 concentration in the blood, regardless of the castration procedure, indicating a potential for the drug to mitigate an inflammatory process unrelated to castration.

Real-time and video-recorded pain assessment in beef cattle: clinical application and reliability in young, adult bulls undergoing surgical castration.

Bovine pain assessment relies on validated behavioral scales related to normal and pain-related behaviors. This study investigated the reliability and applicability of real-time and video-recorded pain assessment, and their agreement, in young, adult bulls undergoing surgical castration. Ten Nelore and nine Angus bulls underwent general anesthesia and surgical castration. Three-minute real-time observations and simultaneous videos were recorded at - 48 h (M0), before sedation, under fasting (M1), after surgery, 3 h after sternal recumbency (M2), after rescue analgesia (M3) and at 24 h (M4). Animals received morphine (after M2), dipyrone (after M3), and flunixin meglumine after surgical castration (M4). Two trained evaluators assessed real-time (n = 95) and video-recorded time-points (n = 95) using the Unesp-Botucatu Cattle Pain Scale (UCAPS). Both assessment methods inferred 'very good' reliability (≥ 0.81) with minimal bias, however, video-recorded assessment (4.33 ± 2.84) demonstrated slightly higher scores compared to real-time (3.08 ± 2.84). The results from this study suggest that UCAPS can be used in real-time or video-recorded to assess pain and guide analgesic therapy in cattle.

A retrospective comparison of postoperative outcomes in ovariectomised jennies (Equus asinus) treated with phenylbutazone or flunixin meglumine.

BACKGROUND: Clinically, flunixin meglumine (FM) and phenylbutazone (PBZ) are preferentially selected for the treatment of visceral and musculoskeletal pain, respectively, in horses. In donkeys, there is no information to support or refute this conventional conjecture. OBJECTIVES: To compare postoperative outcomes in a group of jennies treated with intravenous FM or oral PBZ. ANIMALS: Fourteen jennies unilaterally ovariectomised by standing left flank laparotomy. STUDY DESIGN: Retrospective cohort study. METHODS: Data from medical records of ovariectomised jennies (case details, weight, non-steroidal anti-inflammatory drug [NSAID] protocol, surgery duration, operative sequence, anaesthesia protocol, physical examination findings and outcomes) were collected. From collated data, postoperative adverse events were defined as fever, tachycardia, tachypnea, inappetence, altered mentation, abnormal oral mucous membranes, bruxism, colic, incisional complications (i.e., drainage, oedema, peri-incisional emphysema and pain) and non-survival, then further divided into occurrence during the early (≤24 h) or late (>24 h) postoperative period for data analysis using R software. Chi-squared test was used to compare individual adverse events between groups (PBZ vs. FM) and moments (early vs. late). Significance was set at p ≤ 0.05. RESULTS: PBZ treatment (8/14) was associated with (odds ratio, 95% confidence interval) more total (2.93, 1.97-4.36), early (3.01, 1.87-4.84) and late (2.69, 1.28-5.63) adverse events than FM treatment (6/14). Tachycardia (37.83, 2.21-646.66), tachypnoea (0.29, 0.13-0.66), altered mentation (2.78, 1.01-7.67), altered mucous membranes (18.38, 1.04-325.23), incisional oedema (44.33, 2.60-754.5) and incisional pain (47.78, 2.81-811.61) were significantly different between groups. Early adverse events significantly different between groups included tachycardia (50.2, 2.9-877.0), altered mentation (3.33, 1.08-10.29) and incisional pain (21.0, 1.2-374.5), with late adverse events being tachypnea (0.07, 0.01-0.62), incisional oedema (32.92, 1.85-584.28) and incisional pain (28.92, 1.62-515.68). Colic (2/8) and non-survival (1/8) were rare events that only occurred in the PBZ cohort and could not be further evaluated for differences. MAIN LIMITATIONS: Small sample size; retrospective study; treatment bias; varied administration routes. CONCLUSIONS: Oral PBZ may be inappropriate to use following abdominal surgery in donkeys. CLINICAL RELEVANCE: More prospective and case-controlled studies are needed to evaluate the clinical efficacy of these two NSAIDs in donkeys.

Anti-inflammatory effects of insulin regular and flunixin meglumine on endotoxemia experimentally induced by Escherichia coli serotype O55:B5 in an ovine model.

BACKGROUND: Endotoxemia is a major cause of mortality in large animals and there are several therapeutic regimens for the treatment of endotoxemia. Recent studies have suggested the anti-inflammatory effects of insulin in endotoxemic human and laboratory animal models but to the best of our knowledge there is no report on the possible therapeutic effect of insulin in large animal endotoxemia. OBJECTIVE: This experiment was conducted to evaluate the anti-inflammatory effects of insulin regular compared with flunixin meglumine on the treatment of endotoxemia in sheep. METHODS: Lipopolysaccharide from Escherichia coli was administered intravenously to ewes. Anti-inflammatory effects of flunixin meglumine (at 2.2 mg/kg) and insulin regular (at 1.5 and 3 IU/kg) were evaluated by determination of serum concentrations of acute phase proteins, inflammatory cytokines and oxidative stress biomarkers. RESULTS: Insulin regular at 3 IU/kg controlled the acute phase response following endotoxemia induction. The anti-inflammatory potency of insulin regular at 3 IU/kg was significantly higher than at 1.5 IU/kg and of flunixin meglumine at 2.2 mg/kg (P < 0.05). CONCLUSION: Insulin regular induces its anti-inflammatory effects in a dose-dependent manner. Intravenous use of insulin regular can be a potential new therapeutic regimen for endotoxemia in large animal medicine.

Pharmacokinetics of flunixin meglumine in mature swine after intravenous, intramuscular and oral administration.

BACKGROUND: The purpose of this study was to determine intravenous (IV), intramuscular (IM) and oral (PO) FM PK in mature swine. Appropriate pain management for lameness in swine is a critical control point for veterinarians and producers, but science-based guidance on optimal housing, management and treatment of lameness is deficient. Six mature swine (121-168 kg) were administered an IV, IM, or PO dose of flunixin meglumine at a target dose of 2.2 mg/kg in a cross-over design with a 10 day washout period between treatments. Plasma samples collected up to 48 hours post-administration were analyzed by high pressure liquid chromatography and mass spectrometry (HPLC-MS) followed by non-compartmental pharmacokinetic analysis. RESULTS: No adverse effects were observed with flunixin meglumine administration for all routes. Flunixin meglumine was administered at an actual mean dose of 2.21 mg/kg (range: 2.05-2.48 mg/kg) IV, IM and PO. A mean peak plasma concentration (CMAX) for IM and PO administration was 3748 ng/ml (range: 2749-6004 ng/ml) and 946 ng/ml (range: 554-1593 ng/ml), respectively. TMAX was recorded at 1.00 hour (range: 0.50-2.00 hours) and 0.61 hours (range: 0.17-2.00 hours) after PO and IM administration. Half-life (T ½ λz) for IV, IM and PO administration was 6.29 hours (range: 4.84-8.34 hours), 7.49 hours (range: 5.55-12.98 hours) and 7.08 hours (range: 5.29-9.15 hours) respectively. In comparison, bioavailability (F) for PO administration was 22% (range: 11-44%) compared to IM F at 76% (range: 54-92%). CONCLUSIONS: The results of the present study suggest that FM oral administration is not the most effective administration route for mature swine when compared to IV and IM. Lower F and Cmax of PO-FM in comparison to IM-FM suggest that PO-FM is less likely to be an effective therapeutic administration route.

Pain management with flunixin meglumine at dehorning of calves.

Dehorning (DH) of calves is a common procedure on commercial dairy farms. Pain management of calves has been investigated in several studies. It is generally accepted that the use of local anesthesia before DH is essential for pain management. Postoperative inflammatory pain should be treated by using a nonsteroidal antiinflammatory drug. The objective of this controlled, randomized, and blinded clinical trial was to determine the effects of the nonsteroidal antiinflammatory drug flunixin meglumine before DH on cortisol concentrations in sera of 5- to 9-wk old calves. Furthermore, selected behavioral characteristics and heart and respiratory rate were examined to assess pain in the hours after dehorning. A total of 80 calves were allocated to 4 groups. In each of 20 replicates, 4 calves were randomly assigned to the following groups: in 3 treatment groups, calves received a local anesthetic (10 mL of procain hydrochloride) and a first treatment (i.v.) with flunixin meglumine or a placebo 20 min before hot-iron dehorning, and a second treatment with flunixin meglumine or a placebo (0.9% saline) 3 h after DH. Calves in the control (CON) group were not dehorned and did not receive any treatment. Groups received 2.2 mg of flunixin meglumine/kg followed by a placebo (FP), 2.2 mg of flunixin meglumine/kg for both treatments (FF), or a placebo for both treatments (PP). Blood samples were collected from all calves, including CON calves, 20 min before restraint in a headlock for DH, 2 min after DH, as well as 30 min and 1, 2, 4, 6, and 8 h after DH. Samples were analyzed for concentration of cortisol by enzyme immunoassay. It was found that concentration of cortisol, calculated as area under the curve, was greater in PP compared with FF and tended to be greater compared with FP. Significant differences between PP and FF were detected at 30 min and 2 h after DH. Throughout the observation period, cortisol concentrations were in both flunixin meglumine-treated groups at a similar level as in the CON group. The heart and respiratory rates showed neither difference between the CON group and the 3 dehorned groups nor between the treatment groups.

The pharmacokinetics and effects of meloxicam, gabapentin, and flunixin in postweaning dairy calves following dehorning with local anesthesia.

Approved analgesic compounds in cattle are not currently available in the United States due to the lack of validated pain assessment methods and marker residue depletion studies. In this study, we compared the pharmacokinetic parameters and effect of preemptive analgesics administered to calves subjected to dehorning with local anesthesia. Holstein steers were randomly assigned to receive one of the following treatments per os (PO) or intravenously (IV) (n = 8/group): meloxicam (1 mg/kg PO), gabapentin (15 mg/kg PO), meloxicam (1 mg/kg), and gabapentin (15 mg/kg) PO, flunixin (2.2 mg/kg IV), or a placebo. Plasma drug, haptoglobin, substance P (SP) concentrations, serum cortisol concentrations, ocular thermography, mechanical nociceptive threshold (MNT), and average daily gain (ADG) were evaluated. Data were analyzed using mixed-effects models and noncompartmental pharmacokinetic analysis. Meloxicam, gabapentin, and meloxicam with gabapentin at the present doses did not reduce cortisol concentrations. Analgesic-treated calves had significantly lower plasma SP concentrations and improved ADG compared with controls. Flunixin calves had reduced circulating cortisol compared with controls. Meloxicam-treated calves showed an increase in MNT at two horn bud sites compared with the other treatments. Analgesics improved ADG and reduced biomarkers of pain, but effects differed by compound and route of administration.

Effect of farrowing duration, parity number and the type of anti-inflammatory drug on postparturient disorders in sows: a clinical study.

The aim of the present study was to investigate the effects of farrowing duration, parity number, and type of anti-inflammatory drug used postpartum on the incidence of postparturient disorders in sows. The duration of farrowing and postparturient disorders were examined in 64 sows at Days 0, 1, 2, and 3 after farrowing. The sows were classified according to parity number (1, 2-4, and 5-7), duration of farrowing (<2, 2-2.9, 3-3.9, and 4-8 h), and the type of anti-inflammatory drugs (flunixin méglumine and dipyrone). The farrowing duration was 178.0 ± 73.5 min (2.96 h). The percentage of sows with fever increased from 40 to 100 % when the farrowing duration increased from <2 to 4-8 h. On Day 1 of the postpartum, 93.7 % of primiparous sows had fever, while 52.6 and 47.6 % of sows parity 2-4 and 5-7 had a fever (P<0.05). The presence of vaginal discharge on Day 1 of the postpartum was higher in sows of parity 5-7 than sows of parity 2-4 (85.7 and 52.6 %, P=0.029). The use of flunixin méglumine after parturition in sows reduced the percentage of sows with a fever from 61.3 to 22.6 % within 2 days (P=0.002), while, the percentage of sows with a fever was not decreased in sows treated with dipyrone. It can be concluded that the incidence of postparturient disorders in sows was affected by sow parity, farrowing duration and the type of anti-inflammatory drug used. Sows with a farrowing duration of ≥ 4 h were at a high risk of having fever at Day 1 after parturition.

The effect of supportive E. coli mastitis treatment on PMN chemiluminescence and subpopulations of T lymphocytes.

The aim of this field study was to assess the impact of a single i.m. injection of lysozyme dimer and flunixin meglumine in combination with intramammary and systemic antibiotic on chemiluminescence of PMN (polymorphonuclear leucocytes) and subpopulations of lymphocyte T in blood of cows with E. coli mastitis. Examinations were performed on 30 dairy cows affected with naturally occurring acute form of E. coli mastitis. Cows were randomly divided into three groups according to the method of treatment. The first group was treated with approved intramammary antibiotic product, the same antibiotic in i.m. injection and one injection of flunixin meglumine on the first day of therapy. Next group was treated with the same antibiotic and additionally one injection of lysozyme dimer on the first day of therapy. The third one was treated only with an antibiotic and served as a control group. Blood samples were taken before treatment and on days 3 and 7. In samples haematology indices were determined, spontaneous and opsonised zymosan stimulated CL and PMA measurements were performed and the subpopulations of T lymphocyte (CD2(+), CD4(+), CD8(+)) were assayed in whole blood. There was no effect of the applied supportive treatment on the value of morphological blood indices. A significant influence of the time of sample collection on the level of CL and dynamics of lymphocytes T subpopulation was demonstrated. A single injection of flunixin meglumine or lysozyme dimer on the day of the beginning of treatment of E. coli mastitis, does not affect the level of neutrophil chemiluminescence and the percentage of T lymphocytes in the blood of mastitic cows in the analysed period of time.