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OBJECTIVE To determine the effects of prolonged administration of the oral NSAIDs phenylbutazone and firocoxib on concentrations of cytokines and growth factors in platelet-rich plasma (PRP) and autologous protein solution (APS). ANIMALS 6 adult University owned horses. METHODS Horses were randomized to receive phenylbutazone (1 g, orally, q 12 h) or firocoxib (57 mg, orally, q 24 h) for 6 days. Blood was obtained and processed for APS (Pro-Stride) and PRP (Restigen) before the administration of NSAIDs and at 7 days (1 day following cessation of NSAIDs). Horses underwent a two-week washout period, during which blood was obtained at 14 days and 21 days. The protocol was repeated with a crossover design. PRP and APS were analyzed for concentrations of platelets, leukocytes, and several cytokines (IL-1β, IL-10, IL-6, IL-8, and tumor necrosis factor-α) and growth factors (PDGF, FGF-2, and TGF-β1) using immunoassays. Plasma was evaluated for drug concentrations. RESULTS No significant differences existed in concentrations of growth factors and cytokines before or after prolonged administration of NSAIDs. There were significant differences in concentrations of leukocytes and platelets in PRP compared to APS, with higher concentrations of leukocytes at the day 7 time point (T) in APS (phenylbutazone) and in concentrations of platelets in APS at T0 (firocoxib) and in APS at T7 (phenylbutazone). CLINICAL RELEVANCE Veterinarians can recommend the administration of these oral NSAIDs prior to obtaining blood for PRP and APS provided a single-day washout period is instituted [ABSTRACT FROM AUTHOR]

OBJECTIVE: To evaluate the effects of aging on phenylbutazone (PBZ) disposition in older horses (= 25 years old) compared to young adults (4 to 10 years old) by characterizing the pharmacokinetic profile of PBZ and its active metabolite, oxyphenbutazone (OPBZ), following a 2.2-mg/kg dose, IV. We hypothesized that the disposition of PBZ will be affected by age. ANIMALS: 16 healthy horses (8 young adults aged 4 to 10 years and 8 geriatric horses = 25 years old). METHODS: Horses were administered a single 2.2-mg/kg PBZ dose, IV. Plasma samples were collected at designated time points and frozen at -80 °C until assayed using liquid chromatography-tandem mass spectrometry. Pharmacokinetic analyses were performed using Phoenix WinNonlin, version 8.0 (Certara). Both clinical and pharmacokinetic data were compared between age groups using independent samples t tests, with P < .05 considered significant. RESULTS: Baseline characteristics did not differ between groups, with the exception of age, weight, and plasma total solids. Plasma concentrations of PBZ were best described by a two-compartment model. The maximum plasma concentration of OPBZ was reached at 5 hours for both age groups, and the metabolite-to-parent-drug area-under-the-curve ratios were approximately 20% for both groups. None of the pharmacokinetic parameters of PBZ or its metabolite, OPBZ, differed significantly between age groups. [ABSTRACT FROM AUTHOR]

Aim: to estimate efficacy, tolerability, and safety of Ambenium® parenteral [phenylbutazone sodium 400 mg and lidocaine hydrochloride 4 mg] used for treatment of patients with low back pain. Methods. A total of 100 patients with low back pain (LBP), who received a single intramuscular injection of Ambenium® parenteral, were included in the study. The follow-up period was 3 days. The change in pain severity on VAS (mm) was selected as a primary outcome measure for efficacy. The pain syndrome severity was estimated before administration of the drug (visit 1) and 4, 6, 8 and 12 h after the drug administration, as well as during visits 2 (day 2) and 3 (day 4). The McGill Pain Questionnaire, muscle syndrome index (MSI), Roland-Morris Disability Questionnaire pain estimates were used as the secondary diagnostic criteria. The percentage of patients with the positive response relative to baseline (the decrease in pain severity on VAS by more than 50%) was also determined. Results. The dynamics of the primary efficacy measure (pain severity on VAS) was as follows: 7.4 ± 0.92 cm (mean ± standard deviation) during visit 1, 5.6 ± 1.49 cm after 2 h, 4.6 ± 1.74 cm after 4 h, 3.0 ± 1.79 cm after 8 h; the VAS score was 2.3 ± 1.70 cm after 12 h (р

Mares enrolled in assisted reproductive technologies (ARTs) programs are often treated with non-steroidal anti-inflammatory drugs (NSAIDs), particularly phenylbutazone (Bute), due to chronic lameness. The current study was performed to determine the effect of Bute administration on the developmental competence of in vitro -matured equine oocytes subjected to Intracytoplasmic Sperm Injection (ICSI). In a Preliminary Study, immature cumulus-oocyte complexes (COCs) recovered by post-mortem ovary harvested from two healthy mares (n = 2) treated for 10 days with Bute (4.4 mg/kg, PO, BID), and four non-treated healthy mares (n = 4), were matured in vitro and subjected to Piezo-driven ICSI. Lower oocyte in vitro maturation [Bute: 25% (3/12) vs. Control: 61% (28/46)] and blastocyst rates [Bute: 0% (0/12) vs. Control: 18% (5/28)] were observed in the Bute-treated when compared to the Control mares (P < 0.05). In the Main Experiment, a group of healthy mares (n = 9) received a daily dose of Bute (4.4 mg/kg, orally, SID) for 10 days. A control group of mares (n = 10) was treated with an equal volume of placebo. Mares in both groups were subjected to ultrasound-guided transvaginal oocyte aspiration (TVA) on days 3, 33, and 77 following the last dose of Bute (PT). Recovered COCs from both mare groups were matured in vitro and subjected to Piezo-driven ICSI. By day-3 PT, oocyte in vitro maturation rate was similar between mare groups [Bute: 65% (36/55) vs. Control: 67% (78/116); P > 0.05], while oocyte recovery [Bute: 53% (55/103) vs. Control: 70% (116/166)], cleavage [Bute: 31% (11/36) vs. Control: 62% (48/78)] and blastocyst rates [Bute: [0%] (0/36) vs. Control: 28% (22/78)] were significantly different (P < 0.05). By day 33 PT and 77 PT, differences on oocyte recovery, in vitro maturation, cleavage, and blastocyst rates were not observed between mare groups. In summary, the administration of Bute for 10 consecutive days (4.4 mg/kg, PO, SID, or BID) is associated with a decrease in the ability of immature equine oocytes to undergo in vitro -maturation (Preliminary Study) and develop to the blastocyst stage following ICSI (Preliminary Study and Main Experiment). This negative effect appeared to be transient, as 30- and 77-days post-treatment, no differences on in vitro maturation, cleavage or blastocyst rates were observed. • Oral phenylbutazone impaired in vitro competence of equine oocytes. • Highest dose of phenylbutazone resulted in no blastocyst production after ICSI. • Recommended dose of phenylbutazone had a transient negative effect on blastocyst production after ICSI. • Embryo production was similar to non-treated mares after one month post-treatment with phenylbutazone. [ABSTRACT FROM AUTHOR]

Herein, poly(aniline‐co‐pyrrole) has been synthetized and investigated to adsorb phenylbutazone (PBZ), ceftiofur (CEF) and prednisolone (PRD) in aqueous medium as proof of concept. After proper adsorbent characterization, some studies were carried out in batch process, i. e., contact time, pH, and concentration. The adsorption mechanism has been conducted using kinetic and isothermal models. It was found that the reaction equilibrium was reached in 20 min for all analytes. The best fit for the experimental data were obtained employing the models of dual‐site Langmuir–Freundlich, Fritz–Schlunder and Langmuir, with R2=0.999, 0.952 and 0.974, for PBZ, CEF and PRD, respectively. For PBZ, CEF and PRD, poly(aniline‐co‐pyrrole) provided a Qmax=238.8 mg g−1 and Kmax=0.086 L g−1, Q=0.028 mg g−1 and Kmax=3.258 L g−1, Q=13.66 mg g−1 and KL=0.005 L g−1, respectively. Finally, the copolymer was evaluated in solid phase extraction, which showed recovery around 70 % for PBZ, offering also exciting opportunities for further application in the separation process. [ABSTRACT FROM AUTHOR]

Background: Phenylbutazone (PBZ) is the most commonly used drug to treat symptoms of lameness in horses; however, it is associated with adverse effects such as gastric ulcer syndrome (EGUS). Interestingly, many practitioners prescribe omeprazole (OME) concurrently with PBZ to prevent the development of EGUS. However, the efficacy and safety of this practice in Mongolian horses with chronic lameness remain unknown. Objectives: To evaluate the clinical effects of a combination of PBZ and OME on chronic lameness in Mongolian horses. Study design: Randomised block experimental design. Methods: Eighteen Mongolian horses with lameness score was ≥3 points, were divided into three treatment groups, with six horses in each group: placebo (CON), PBZ (4.4 mg/kg PO q. 24 h), or PBZ plus OME (4 mg/kg PO q. 24 h; PBZ + OME) in a randomised block design based on the initial lameness score. The horses were treated for 15 days. During this period, weekly gastroscopy, and physiological and biochemical tests were performed. Results: Both PBZ (median 1.0, interquartile range [IQR]: 0.8–1.3; p = 0.01) and PBZ + OME (median 1.0, IQR: 1.0–1.0; p = 0.01) significantly decreased the lameness score compared with before administration. In addition, PBZ significantly increased the equine glandular gastric disease (EGGD) score (3.0 ± 0.6, p < 0.001), GT‐17 content (293.4 ± 21.8 pg/mL, p < 0.001), and pepsinogen‐1 (PG1) content (295.3 ± 38.3 ng/mL, p < 0.001) compared with CON or PBZ + OME. However, it significantly reduced the total protein (53.6 ± 1.5 g/L, p < 0.05) and albumin (25.5 ± 1.8 g/L, p < 0.05) contents. Nevertheless, compared with PBZ, PBZ + OME significantly decreased the EGGD score (0.3 ± 0.5, p < 0.001) and significantly increased the gastric fluid pH (7.3 ± 0.5, p < 0.001), total protein content (62.5 ± 4.6 g/L, p = 0.009), and albumin content (29.4 ± 1.1 g/L, p = 0.004). Meanwhile, they significantly diminished the gastrin 17 (GT‐17) (162.0 ± 21.0 pg/mL, p < 0.001) and PG1 (182.4 ± 22.5 ng/mL, p < 0.001) contents. Main limitations: Individual differences in horses were larger, but the sample size was small. There was larger interval between observations for each index. Conclusions: Compared with PBZ alone, PBZ + OME had no therapeutic effect on chronic lameness; however, it reduced the occurrence of EGGD in Mongolian horses. Horses may be protected against chronic lameness and PBZ‐induced EGGD by increasing the pH value, decreasing serum PG1 and GT‐17 content, and preventing the reduction of myeloperoxidase content. [ABSTRACT FROM AUTHOR]

Suxibuzone is a prodrug of the nonsteroidal anti-inflammatory drug phenylbutazone. The aim of this study was to investigate the nephrotoxicity of suxibuzone using the recommended dosage in euhydrated horses. Serum creatinine levels were used to monitor for the presence of acute kidney injury (AKI) in 11 systemically healthy horses treated orally with suxibuzone at the recommended dosage for five days. Symmetric dimethylarginine (SDMA), urine gamma glutamyl transferase/urine creatinine, fractional excretion of sodium, urine protein-to-creatinine ratio, and urine sediment were assessed as additional monitoring parameters. A significant increase in creatinine was found in treated horses (P = 0.002), 27% (3/11) of treated horses were classified as having AKI compared to 0% of controls (0/10), and a strong correlation was found between the change in creatinine and the change in SDMA in treated horses (t = 0.645, P = 0.012). The results of this study suggest that treatment with suxibuzone at the recommended dosage can induce AKI even in systemically healthy euhydrated horses. [ABSTRACT FROM AUTHOR]

Background: Phenylbutazone is often prescribed to manage pain caused by hyperinsulinemia‐associated laminitis, but in diabetic people nonsteroidal anti‐inflammatory drugs increase insulin secretion and pancreatic activity. Hypothesis/Objectives: Investigate the effect of phenylbutazone administration on insulin secretion in horses. It was hypothesized that phenylbutazone will increase insulin secretion in horses with insulin dysregulation (ID). Animals: Sixteen light breed horses, including 7 with ID. Methods: Randomized cross‐over study design. Horses underwent an oral glucose test (OGT) after 9 days of treatment with phenylbutazone (4.4 mg/kg IV q24h) or placebo (5 mL 0.9% saline). After a 10‐day washout period, horses received the alternative treatment, and a second OGT was performed. Insulin and glucose responses were compared between groups (ID or controls) and treatments using paired t test and analyses of variance with P <.05 considered significant. Results: In horses with ID, phenylbutazone treatment significantly decreased glucose concentration (P =.02), glucose area under the curve (2429 ± 501.5 vs 2847 ± 486.1 mmol/L × min, P =.02), insulin concentration (P =.03) and insulin area under the curve (17 710 ± 6676 vs 22 930 ± 8788 μIU/mL × min, P =.03) in response to an OGT. No significant effect was detected in control horses. Conclusion and Clinical Importance: Phenylbutazone administration in horses with ID decreases glucose and insulin concentrations in response to an OGT warranting further investigation of a therapeutic potential of phenylbutazone in the management of hyperinsulinemia‐associated laminitis beyond analgesia. [ABSTRACT FROM AUTHOR]

The ovine respiratory complex (ORC) is one of the most common respiratory diseases observed in sheep. The objective of the present investigation was to evaluate the comparative therapeutic efficacy of two non-steroidal antiinflammatory drugs (meloxicam and phenylbutazone) for the treatment of the ORC. For this purpose, 33 Ossimi sheep were randomly assigned into three treatment groups (11 each). Group 1 was treated with amoxicillin longacting (LA) and meloxicam, group 2 received amoxicillin LA and phenylbutazone, and group 3 was treated with amoxicillin LA alone. Sheep were examined clinically and clinical index scores were recorded before and after treatment. Additionally, blood samples were collected from each sheep. After 14 days of treatment, sheep of group 1 indicated significant improvements in their clinical index scores and a reduction in total leukocyte count. However, there was a significant increase in red blood cell count, hemoglobin, and MCHC%. There was a significant decrease in the serum globulin, copper, and haptoglobin in group 1, compared to sheep of groups 2 and 3. Based on the results of this study, administering meloxicam to sheep with an ovine respiratory complex resulted in significant improvements in clinical outcomes and significant corrections in above mentioned hematological and biochemical parameters. Although phenylbutazone proved to be less effective, it still demonstrated some degree of efficacy in treating this condition. This study suggests that meloxicam may be a more effective treatment option for ORC with phenylbutazone. [ABSTRACT FROM AUTHOR]

Abstract Background Right dorsal colitis (RDC) is a nonsteroidal anti‐inflammatory drug (NSAID) induced, protein losing enteropathy in horses associated with a high case fatality rate. Objectives To describe signalment, NSAID usage, clinical presentations, clinical pathology, ultrasonographic findings, treatments, outcomes, and factors associated with survival in horses diagnosed with RDC. Animals Thirty‐five horses from 7 Australian equine hospitals diagnosed with RDC. Methods Retrospective case series. Clinical records of cases were accepted if definitively or presumptively diagnosed by an internist with RDC and had ≥3 of: hypoproteinemia or hypoalbuminemia; diarrhea with negative test results for infectious diseases; colic for which other diseases were excluded or right dorsal colon thickening on ultrasound. Descriptive data analysis was performed for categorical and continuous variables. Univariate binominal logistic regressions were used to assess factors associated with survival. Results An overdose of NSAIDs occurred in 84% (21/25) cases where dose was known. Common clinical presentations included diarrhea (69%; 22/32), colic (61%; 20/33), and tachycardia (53%, 17/32). Common clinicopathological findings included hypoalbuminemia (83%; 26/31), hypocalcaemia (79%, 23/29), and hyperlactatemia (77%, 14/18). The right dorsal colon wall appeared subjectively thickened in 77% (24/31) cases using ultrasonography. Case fatality rate was 43% (15/35). Odds of survival significantly decreased with increasing heart rate (odds 0.84, 95% CI = 0.71‐0.92, P = .01), packed cell volume (odds 0.91, 95% CI 0.82‐0.98, P = .05) and abnormal appearance of mucous membranes (odds 0.05, 95% CI 0.005‐0.28, P = .001) on hospital presentation. Conclusions and Clinical Importance An overdose of NSAIDs is common in horses diagnosed with RDC. Serum albumin concentrations should be monitored in horses receiving a prolonged course of NSAIDs. Overall prognosis for RDC remains fair.

Background: Treatment with phenylbutazone (nonselective COX inhibitor) decreases the diuretic and natriuretic effects of furosemide by nearly 30% but the effects of COX‐2 specific inhibitors (firocoxib) and atypical NSAIDs (dipyrone) are unknown. Hypothesis: Furosemide‐induced diuresis after pretreatment with firocoxib or dipyrone is diminished to a lesser extent than after pretreatment with phenylbutazone. Animals: Eight healthy mares. Methods: Each mare received 4 treatments in a prospective experimental crossover study using a replicated 4 × 4 Latin Square design: furosemide alone (FU), furosemide and phenylbutazone (PB), furosemide and firocoxib (FX), and furosemide and dipyrone (DP). After 24 hours of NSAID treatment at recommended dosages, ureteral catheters were placed for continual urine collection. After a 30‐minute baseline collection period, furosemide (1.0 mg/kg, IV) was administered, and urine and blood samples were collected for 4 hours. Data were assessed by repeated measures ANOVA. Results: Four‐hour urine volume was (mean ± SD) ~25% less (P <.001) after pretreatment with all NSAIDs (PB 19.1 ± 2.1 mL/kg, FX 17.7 ± 3.5 mL/kg, DP 19.1 ± 3.9 mL/kg), as compared to FU (23.4 ± 5.1 mL/kg) (P <.001), but there were no differences between PB, FX, or DP. Interindividual variability in furosemide diuresis after pretreatment with different NSAIDs was observed. Conclusions and Clinical Importance: Though COX‐2 selective NSAIDs and dipyrone might have less severe or fever gastrointestinal adverse effects in horses, our data suggest minimal differences in effects on furosemide‐induced diuresis, and possibly, risk of nephrotoxicosis. [ABSTRACT FROM AUTHOR]

Background: Right dorsal colitis (RDC) is a nonsteroidal anti‐inflammatory drug (NSAID) induced, protein losing enteropathy in horses associated with a high case fatality rate. Objectives: To describe signalment, NSAID usage, clinical presentations, clinical pathology, ultrasonographic findings, treatments, outcomes, and factors associated with survival in horses diagnosed with RDC. Animals: Thirty‐five horses from 7 Australian equine hospitals diagnosed with RDC. Methods: Retrospective case series. Clinical records of cases were accepted if definitively or presumptively diagnosed by an internist with RDC and had ≥3 of: hypoproteinemia or hypoalbuminemia; diarrhea with negative test results for infectious diseases; colic for which other diseases were excluded or right dorsal colon thickening on ultrasound. Descriptive data analysis was performed for categorical and continuous variables. Univariate binominal logistic regressions were used to assess factors associated with survival. Results: An overdose of NSAIDs occurred in 84% (21/25) cases where dose was known. Common clinical presentations included diarrhea (69%; 22/32), colic (61%; 20/33), and tachycardia (53%, 17/32). Common clinicopathological findings included hypoalbuminemia (83%; 26/31), hypocalcaemia (79%, 23/29), and hyperlactatemia (77%, 14/18). The right dorsal colon wall appeared subjectively thickened in 77% (24/31) cases using ultrasonography. Case fatality rate was 43% (15/35). Odds of survival significantly decreased with increasing heart rate (odds 0.84, 95% CI = 0.71‐0.92, P =.01), packed cell volume (odds 0.91, 95% CI 0.82‐0.98, P =.05) and abnormal appearance of mucous membranes (odds 0.05, 95% CI 0.005‐0.28, P =.001) on hospital presentation. Conclusions and Clinical Importance: An overdose of NSAIDs is common in horses diagnosed with RDC. Serum albumin concentrations should be monitored in horses receiving a prolonged course of NSAIDs. Overall prognosis for RDC remains fair. [ABSTRACT FROM AUTHOR]

The in vivo metabolism and pharmacokinetics of flunixin meglumine and phenylbutazone have been extensively characterized; however, there are no published reports describing the in vitro metabolism, specifically the enzymes responsible for the biotransformation of these compounds in horses. Due to their widespread use and, therefore, increased potential for drug-drug interactions and widespread differences in drug disposition, this study aims to build on the limited current knowledge regarding P450-mediated metabolism in horses. Drugs were incubated with equine liver microsomes and a panel of recombinant equine P450s. Incubation of phenylbutazone in microsomes generated oxyphenbutazone and gamma-hydroxy phenylbutazone. Microsomal incubations with flunixin meglumine generated 5-OH flunixin, with a kinetic profile suggestive of substrate inhibition. In recombinant P450 assays, equine CYP3A97 was the only enzyme capable of generating oxyphenbutazone while several members of the equine CYP3A family and CYP1A1 were capable of catalyzing the biotransformation of flunixin to 5-OH flunixin. Flunixin meglumine metabolism by CYP1A1 and CYP3A93 showed a profile characteristic of biphasic kinetics, suggesting two substrate binding sites. The current study identifies specific enzymes responsible for the metabolism of two NSAIDs in horses and provides the basis for future study of drug-drug interactions and identification of reasons for varying pharmacokinetics between horses.

In a parallel, double-blind and randomized trial of 6-weeks' duration, phenylbutazone (150 mg to 300 mg daily) was compared with indomethacin (75 mg to 100 mg daily) in the management of 26 patients with active ankylosing spondylitis. None of the patients in either group withdrew from the study because of lack of eficacy of the drugs. Both drugs were equally effective in the relief of pain and tenderness of the afected joints. Overall subjective improvement, assessed by the patient and the investigator at the end of the trial, was present in 90% of the patients in the phenylbutazone group and in 75% of those in the indomethacin group. The mean values of all the spinal motion tests improved in the phenylbutazone group but not in the indomethacin group. Statistically signijkuant improvement in the Schober test was achieved in the phenylbutazone group and in chest expansion in the indomethacin group. Characteristic untoward effects related to the central nervous system and gastro-intestinal tract were present in a few patient in both groups.(5). [ABSTRACT FROM AUTHOR]

BackgroundPain management is critical to equine welfare with non-steroidal anti-inflammatory drugs (NSAID) commonly used in horses. However, systemic NSAID use is limited by harmful gastrointestinal and renal side effects. Intravenous regional limb perfusion (IVRLP) is a technique used in horses that produces high, local antibiotic concentrations while limiting systemic circulation. NSAID-IVRLP would be a novel method of local pain management while limiting systemic NSAID side effects. To date, NSAID-IVRLP administration has not been reported in horses. This study aimed to identify the pharmacokinetics and local complications associated with using the NSAID phenylbutazone (PBZ) for IVRLP in six standing adult horses.MethodsPBZ-IVRLP, at a dose of 2.2 mg/kg PBZ, was performed in a randomly assigned forelimb cephalic vein in 6 standing, healthy adult horses. A placebo-IVRLP was performed in the contralateral forelimb for comparison. Systemic serum and radiocarpal joint synovial fluid PBZ concentrations were identified at various timepoints (before IVRLP T-0 h, just after tourniquet removal T-0.5, 1.5, 3, 5, 12, 16, and 24 h post IVRLP) for non-compartmental pharmacokinetic analysis and concentration over time curves. Local complications associated with PBZ-IVRP were evaluated for up to 7 days following PBZ-IVRLP using physical and ultrasonographic assessment. On day 7 horses were humanely euthanized with histology performed on both forelimbs at PBZ-IVRLP and placebo-IVRLP administration sites.ResultsNon-compartmental pharmacokinetics for PBZ, and its major metabolite oxyphenbutazone (OBZ), were determined for serum and synovial fluid. Synovial PBZ concentrations (mean ± SD; 1.9 ± 2.1 μg/mL) were significantly lower (p = 0.03; CI,0.46–7.36) than serum PBZ concentrations (5.8 ± 5.1 μg/mL) at any time point. Physical and ultrasonographic measurements were not significantly different between PBZ- and placebo-IVRLP forelimbs. The most common histologic findings included focal deep dermal/subcutaneous hemorrhage and edema. Two horses showed perivasculitis and one horse showed a resolving thrombus in the cephalic vein of the PBZ-IVRLP limb. This horse also had severe perivasculitis and fibrinosuppurative dermatitis/panniculitis in the placebo-IVRLP limb.ConclusionPBZ-IVRLP pharmacokinetics at a 2.2 mg/kg dose showed no benefit compared to systemic PBZ administration in standing adult horses. Local complications associated with PBZ-IVRLP were similar to placebo-IVRLP on physical and ultrasonographic evaluation.

Objectives: To investigate if hepatitis A virus cell receptor 1/kidney injury molecule 1 (HAVCR1/KIM1) in urine is detectable concurrently with increases in serum creatinine concentrations in horses receiving a recommended dose of phenylbutazone (PBZ) for 7 days. Design: Preliminary study. Methods: Ten clinically healthy horses with normal physical examination and laboratory work were randomly assigned to PBZ or placebo groups (5 each). The PBZ group received PBZ at 4.4 mg/kg mixed with corn syrup orally every 12 hours. The placebo group received corn syrup orally every 12 hours. Both groups were treated for 7 days. Kidney ultrasonography was performed, and venous blood and urine samples were collected prior to commencement and at the end of treatment. Samples from 1 additional healthy horse, 3 horses with acute kidney failure, and 1 horse with chronic kidney failure were also evaluated. Results: None of the 10 horses had detectable HAVCR1/KIM1 in urine at baseline. Serum creatinine concentrations in placebo group did not increase, and HAVCR1/KIM1 was undetectable in urine. At the end of treatment, 3 of 5 horses receiving PBZ developed increases in serum creatinine of >26.5 μmol/L (>0.3 mg/dL), and HAVCR1/KIM1 was detectable in urine, despite normal findings on kidney ultrasonography in all horses. Conclusions: HAVCR1/KIM1 is detectable in urine and is associated with increases in serum creatinine concentrations of >26.5 μmol/L in horses following treatment with PBZ for 7 consecutive days. Thus, HAVCR1/KIM1 might aid in the early detection of acute kidney injury in horses. [ABSTRACT FROM AUTHOR]

The present study aims to investigate the influence of dexamethasone administration on the pharmacokinetics of phenylbutazone and its plasma concentration as well as its pharmacological interaction in a chick model. The analgesic median effective doses (ED50s) of phenylbutazone and dexamethasone are separately evaluated as 5.60 and 0.63 mg/kg, IP, and their ED50s are estimated and reduced to 1.76 and 0.19 mg/kg, IP, respectively. The type of pharmacological interaction between phenylbutazone and dexamethasone is synergistic as determined by the isobolographic analysis. The phenylbutazone administration at 11.20 mg/kg, IP has plasma concentrations of 39.83, 66.17, 48.00, 35.30, 26.50 and 13.33 µg/ml in the estimated times of 0.25, 0.5, 1, 2, 4, and 24 hours, respectively. These concentrations are increased to 57.00, 384.17, 210.67, 138.67, 65.50 and 50.10 µg/ml as dexamethasone 1.26 mg/kg, IP is given by 43, 426, 339, 293, 147 and 276%. Phenylbutazone pharmacokinetics are increased and result in an elevation in an area under the curve (AUC0-∞) 196%, area under the moment curve (AUMC0-∞) 140%, elimination rate constant (Kel) 50%, and maximum concentration (Cmax) 426%. However, other parameters are reduced to include half-life (t1/2β) 33%, mean residence time (MRT) 18%, steady state of the volume of distribution (Vss) 78%, and clearance (Cl) 60%. The overall findings reveal a synergism as a type of pharmacological interaction between phenylbutazone and dexamethasone. In addition, a change in phenylbutazone pharmacokinetics and its plasma concentration which improves phenylbutazone therapeutic efficiency in the chick model is noticed.

The reason for the recent study was to inspect the therapeutic efficacy of meloxicam and phenylbutazone alone with their analgesic interaction and their subsequent inhibitory interaction at the level of cyclooxygenase-2 in mice. Meloxicam and phenylbutazone had the analgesic-median effective doses (ED50s) of 15.57 and 119.73 mg/kg, i.p., respectively, given once to mice separately as determined by the up-and-down procedure using a hot plate method. The estimated analgesic ED50s for meloxicam and phenylbutazone combination were at 12.84 and 98.75 mg/kg, i.p., correspondingly when given together at a ratio of 1:1 of their ED50s. The isobolographic analysis reveals that the analgesic interaction between meloxicam and phenylbutazone was antagonistic, as indicated by the interaction index of 1.65. The ELISA technique was used to estimate the cyclooxygenase-2 activity, reflecting that meloxicam or phenylbutazone significantly inhibited the cyclooxygenase-2 activity by 72 and 90%, respectively, compared to the control group. The combination composed of meloxicam and phenylbutazone has a lower limit of inhibition of the cyclooxygenase-2 activity (33%) in comparison to meloxicam or phenylbutazone. Meloxicam and phenylbutazone coadministration were significantly different from the control, meloxicam, and phenylbutazone groups concerning the cyclooxygenase-2 activity in mice. The sum of the data concluded that meloxicam and phenylbutazone have an excellent analgesic efficacy when administered alone. In contrast, the mixture of these two drugs has no benefit because of the antagonistic interaction at cyclooxygenase-2 in mice.

The electrochemical performance of phenylbutazone (PBZ) was studied using a multi-walled carbon-nanotube-modified paste electrode (MWCNT/CPE) using a variety of voltammetric tools like cyclic voltammetry (CV), linear sweep voltammetry (LSV), and square wave voltammetry (SWV). The results showed that the MWCNT/CPE exhibited remarkable electro-catalytic action towards the electrochemical oxidation of PBZ in a phosphate buffer solution of physiological pH 7 compared to a bare carbon paste electrode. The electro-kinetic parameters like heterogeneous rate constant, transfer coefficient, scan rate, pH, and involvement of electrons in electro-oxidation of PBZ was investigated. For bare CPE, the peak current was noted to be 19.53 μ A with peak potential of 0.6871 V. For MWCNT/CPE, the peak current was 30.53 μ A with peak potential of 0.6792 V. The anodic peak was analyzed, and the process was diffusion controlled. For the estimation of PBZ, a SWV technique was developed with great precision and accuracy, with a detection limit of 5.2 nM and a limit of quantification of 17 nM, in the concentration range 1 × 10 ^−7 to 10 × 10 ^−6 M. The MWCNT/CPE has been used successfully for PBZ detection in injection, blood, and urine samples, with recovery rates of 98.9% to 101.5%, 96.3% to101.7% and 98.3% to 102.8%, respectively.

• Two site II-targeting probes were designed with full consideration of their binding to HSA. • TAB2/6 displayed favorable selective HSA sensitivity and strong HSA binding ability. • WP5-TAB2/6 complex inherited the responsiveness and binding ability of the probe. • WP5-TAB2/6 complex self-assembled into a vesicular supramolecular fluorescent probe. • The supramolecular probe could be used for HSA-mediated cell imaging and drug delivery. Two cationic probes (named TAB2 and TAB6) specifically for binding to site II in human serum albumin (HSA) were designed and synthesized. Both probes exhibited selective fluorescence "turn-on" responsiveness to site II in HSA, though minor differences in their cationic terminals resulted in notable variations in their albumin responsiveness. TAB2 and TAB6 also exhibited strong binding affinity toward HSA. The presence of phenylbutazone, ibuprofen, and lidocaine had minimal impact on the albumin responsiveness of these probes. Furthermore, the complex formed by TAB2/6 and water-soluble pillar[5]arene (WP5) showed enhanced HSA site II-targeting fluorescence responsiveness. More importantly, the WP5-TAB2/6 complex self-assembled into vesicular supramolecular probes in aqueous solution (pH=7.4). Those supramolecular probes were promising for HSA-mediated cell imaging and act as a pH-sensitive drug-delivery platform to enhance the anticancer efficiency of doxorubicin (DOX). [Display omitted] [ABSTRACT FROM AUTHOR]

The paper presents a novel pine bark based biosorbent for solid-phase extraction (SPE). The morphology and composition of the pine bark were characterized using Fourier transform infrared spectroscopy (FTIR) and scanning electron microscopy (SEM). The biosorbent was used for the preparation of wastewater for the determination of phenylbutazone, sulfamethazine, carbendazim, and linuron by high performance liquid chromatography with ultraviolet detection (HPLC-UV). The SPE conditions were optimized with respect to elution solvent, sample volume, and extraction pH. The results showed that developed sorbent provides good repeatability. The relative standard deviation (n = 3), was between 0.3 and 2.2%. The limits of detection (LOD) were between 0.11 and 0.4 µg.L−1. The developed method was used for determination of the analytes in effluent from a wastewater treatment plant. [ABSTRACT FROM AUTHOR]

The administration of prohibited substances has been used in agricultural show competitions and animal racing industries to gain unfair competitive advantages. We report the first large prospectively designed descriptive study of drug testing in four species (n  = 1,598) over a 23 year period. 4.7% of tested exhibits returned positive results. Commonly detected substances included legitimate veterinary therapeutics such as the sedative acepromazine and the non-steroidal anti-inflammatory phenylbutazone. Targeted testing was more likely to return a positive result than random screening (50 vs 4.7% respectively) although numbers in this targeted sample were small (n  = 12). Random drug testing programs were successful in detecting the minority of exhibits using prohibited substances although a wide variety of drugs were found to be used. Further vigilance and research is required in an ever-changing competitive climate to remain at the forefront of detecting new medications in animal show competitions. [ABSTRACT FROM AUTHOR]

Among the causes of lameness in horses, those of arthrogenic origin, especially synovitis, which can progress to advanced joint damages, such as osteoarthritis, are of importance in clinical practice. In this study, we aimed to evaluate the early diagnosis, treatment, and treatment outcomes of acute synovitis, which occur frequently in English and Arabian horses during the racing season. A total of 167 joints of 126 horses (39 English and 87 Arabian Thoroughbred) aged 2-4 years diagnosed with acute synovitis were evaluated using clinical, radiographic, and ultrasonographic examinations. The treatment protocol of horses consisted of cold hydrotherapy and light pressure bandage initially, followed by rest for 10 days and controlled walking only, a single dose of phenylbutazone, and intra-articular corticosteroid and hyaluronic acid injection. Although functional improvement was observed in all the horses following this treatment, subsequent relapses occurred in 22 cases. Consequently, it is important to comply with this treatment program and plan the treatment of acute synovitis in the early period. Controlled gaits, rather than absolute immobility, increase the success of treatment, especially in horses at rest. In addition, it is important to ensure that the relevant joint is not overburdened after the rest period in order to avoid relapses. [ABSTRACT FROM AUTHOR]

A 41-year-old woman with no significant past medical history presented to the hospital with complaints of nausea, vomiting, and generalized weakness over two weeks. The patient did not seek medical attention as she assumed that her symptoms willwould resolve. Following her initial denial of drug abuse and her abnormal urine drug screening, we discussed the findings with the patient. She later admitted to using both amphetamines and marijuana. This led us to take a detailed social history that revealed an unexpected event.

Antimicrobial resistance has been an increasingly serious threat to global public health. The contribution of non-antibiotic pharmaceuticals to the development of antibiotic resistance has been overlooked. Our study found that the anti-inflammatory drug phenylbutazone could protect P. aeruginosa against antibiotic mediated killing by binding to the efflux pump regulator MexR. In this study, antibiotic activity against P. aeruginosa alone or in combination with phenylbutazone was evaluated in vitro and in vivo. Resazurin accumulation assay, transcriptomic sequencing, and PISA assay were conducted to explore the underlying mechanism for the reduced antibiotic susceptibility caused by phenylbutazone. Then EMSA, ITC, molecular dynamic simulations, and amino acid substitutions were used to investigate the interactions between phenylbutazone and MexR. We found that phenylbutazone could reduce the susceptibility of P. aeruginosa to multiple antibiotics, including parts of β-lactams, fluoroquinolones, tetracyclines, and macrolides. Phenylbutazone could directly bind to MexR, then promote MexR dissociating from the mexA - mexR intergenic region and de-repress the expression of MexAB-OprM efflux pump. The overexpressed MexAB-OprM pump resulted in the reduced antibiotic susceptibility. And the His41 and Arg21 residues of MexR were involved in the phenylbutazone-MexR interaction. We hope this study would imply the potential risk of antibiotic resistance caused by non-antibiotic pharmaceuticals. [Display omitted] • Non-antibiotic PBZ could protect P. aeruginosa against antibiotic mediated killing • PBZ could bind to MexR in P. aeruginosa • PBZ lead to the dissociation between MexR and the intergenic region of mexA - mexR • The de-repressed expression of MexAB-OprM efflux a variety of antibiotics • His41 and Arg21 residues of MexR were involved in the ligand-protein interaction [ABSTRACT FROM AUTHOR]

Southern white rhinoceros (Ceratotherium simum simum) frequently develop painful conditions, such as traumatic injuries or osteoarthritis, necessitating the administration of pain‐relieving medications. One of the preferred treatments is the nonsteroidal anti‐inflammatory drug phenylbutazone because of the availability of oral formulations and the familiarity of its use in horses. For the main study, a single oral dose of phenylbutazone at 2 mg/kg was administered to healthy adult rhinoceros (n = 33) housed at six North American zoological institutions. Each rhinoceros had up to four blood samples collected under voluntary behavioural restraint at up to four predetermined time points (0, 1, 1.5, 2, 3, 4, 6, 8, 10, 24, 30 and 48 h). Drug analysis was performed by high‐performance liquid chromatography. The population pharmacokinetic parameters were calculated with nonlinear mixed‐effects modelling, and analysis showed a peak concentration (CMAX) of 3.8 µg/ml at 1.8 h and an elimination half‐life of 9 h. The concentrations achieved were similar to what has been reported for horses and were within the half maximal effective concentration for horses for at least 10 h. A multi‐dose trial in five rhinoceros receiving 2 mg/kg orally once daily for five days found mild accumulation at a predicted factor of 1.2. This study represents the first pharmacokinetic data of phenylbutazone in any rhinoceros species. [ABSTRACT FROM AUTHOR]

Diclofenac, a non-steroidal anti-inflammatory (NSAID), was the cause of the rapid vulture population decline in the Indian subcontinent in the 1990s. Since 2013, diclofenac has been approved for veterinary use in Spain. The Iberian Peninsula (Portugal and Spain) hosts more than 95% of the Old World vulture population in Europe, so this situation poses a significant potential threat for European vultures. Other NSAIDs may also pose a risk to vultures, but a thorough review of available evidence has not been conducted. We conducted a scoping review to analyze the published research on the impact of NSAIDs to Old World vultures to ultimately use the synthesized information to inform risk assessments. We implemented a search strategy of four bibliographic databases (1990–2019). Publications were screened in two steps, and two reviewers independently extracted data relevant to the phases of a risk assessment (release, exposure, and consequences). Among the 78 studies included in the review, 41% focused on India, 21.8% studied the White-rumped Vulture (Gyps bengalensis), 38.5% evaluated diclofenac, and 12.8% meloxicam. There was substantial evidence that diclofenac can lead to mortality in Old World vultures. There was also some evidence of mortality and clinical signs caused by carprofen, ketoprofen, and flunixin meglumine. Mild clinical signs were reported for phenylbutazone, and nimesulide, and no consequences were reported for meloxicam. However, the effects of all these other NSAIDs to vultures need further research. [ABSTRACT FROM AUTHOR]