Search Results (13)

The issue of stray cats and dogs is a global concern with considerable implications for animal welfare and public health. This review aims to provide an updated and comprehensive analysis of non-surgical contraceptive methods tested in studies controlled in vivo in feline and canine females. Immunocontraception via vaccination against gonadotropin-releasing hormone (GnRH), the luteinizing hormone receptor, zona pellucida proteins, and sperm, or use of viral-vectored delivery, is yet developing. Hormonal treatment (progestins, androgens, or GnRH) analogs act directly to block the reproductive axis. However, it produced essential side effects. Analogs of kisspeptin, non-steroid anti-inflammatory drugs such as firocoxib, and delivery of cytotoxins to the pituitary have shown non-conclusive results. Additional methods have also been tested, such as intraovarian injection of necrosing compounds or intravaginal and intrauterine devices. At present, neither of these methods offers permanent sterility that can replace surgical sterilization techniques. To our knowledge, none are currently authorized by the Food and Drug Administration (FDA) or the European Medicines Agency (EMA) for contraceptive methods or sterilization of cats or dogs. Therefore, it is necessary to continue the development of a compound that warrants the sterility of cats and dogs. Full article

Very few studies, often with very small cohorts, have proven chemotherapy efficacy against canine aggressive mammary carcinomas, either in terms of metastasis or median survival, in dogs after surgery and chemotherapy, with such outcomes not being confirmed by other studies. As a result, we lack efficient standardized protocols, which exist in human cases, according to the grade and stage of the tumor in dogs. In this case report, we describe a relapsing grade III solid mammary carcinoma evolving into prominent lymphatic intravascular invasion with multifocal nodal extension (stage IV); we applied an intensive treatment combining radical surgery and intensive adjuvant chemotherapy. The latter combined carboplatin maximal-tolerated-dose chemotherapy, with doses adjusted as necessary, and metronomic chemotherapy with firocoxib, toceranib and chloraminophene, progressively administered and carefully monitored. Adapting the doses prevented adverse events and resulted in 218 days of survival with good quality of life. To our knowledge, this is the first description of such a treatment combination. Our result should be confirmed with a large-scale prospective study. Full article

(1) Background: There is a lack of knowledge about how a single dose of COX-2 selective non-steroidal anti-inflammatory drugs (NSAIDs) might affect the release of growth factors (GFs) and cytokines from canine platelet-rich gels (PRGs) and other hemocomponents. (2) Methods: A crossover study was conducted in six adult mongrel dogs. Animals were randomized to receive a single dose of either carprofen or firocoxib. PRG, temperature-induced platelet lysate (TIPL), chemically induced PL (CIPL), and plasma hemocomponents were obtained from each dog before (1 h) and after (6 h) the treatments. Platelet and leukocyte counts and determination of the concentrations of platelet-derived growth factor-BB, (PDGF-BB), transforming growth factor beta-1 (TGF-β₁), interleukin 1 beta (IL-1β), tumor necrosis factor-alpha (TNF-α) and IL-10 concentrations were assayed by ELISA in all hemocomponents. (3) Results: Both platelet and leukocyte counts and PDGF-BB concentrations were not affected by NSAIDs and time. Total TGF-β₁ concentrations were not affected by NSAIDs; however, the release of this GF was increased in PRG supernatants (PRGS) at 6 h. IL-1β and TNF-α concentrations were significantly (p < 0.001) lower in both firocoxib PRGS and plasma at 6 h, respectively. IL-10 concentrations were significantly (p < 0.001) lower at 6 h in all hemocomponents treated with both NSAIDs. (4) Conclusions: The clinical implications of our findings could indicate that these drugs should be withdrawn from patients to allow their clearance before the clinical use of PRP/PRG. On the other hand, the prophylactic use of NSAIDs to avoid the inflammatory reactions that some patients might have after PRP/PRG treatment should be performed only in those animals with severe reactive inflammation to the treatment. Full article

Non-steroidal anti-inflammatory drugs (NSAIDs) represent one of the most commonly used classes of drugs in both human and veterinary medicine. However, many clinical side effects have been observed, especially when treatment has been prolonged. While the anti-inflammatory efficacy and safety of repeated administration of firocoxib (Previcox^®), which is a selective NSAID COX-2 inhibitor, has been evaluated for short-term use (one to fourteen days), its clinical relevance for longer-term use is not known. As a preliminary study, healthy, adult male and female horses (n = 7) were treated with firocoxib for 40 days concomitant with the collection of blood samples encompassing treatment to assess hematological and biochemical endpoints. Daily oral administration of firocoxib was performed with one 57 mg tablet/animal (0.11–0.14 mg/kg), which was crushed and mixed with feed. Blood samples were collected one day before treatment (D0 or basal sample), during (D10, D20, D30, and D40), and after treatment (D55 and D70). Results indicated some hematological and biochemical effects were significantly reduced (p < 0.05) towards the end of treatment on D40 relative to pre-treatment or baseline values on D0. Post-treatment, all values returned to pre-treatment values within 30 days without any apparent clinical adversities. In conclusion, while these preliminary results are favorable for prolonged use of firocoxib in horses, future studies are required to evaluate the efficacy of prolonged use accompanied with other clinically relevant endpoints in healthy as well as injured or diseased animals. Full article

Veterinarians face the lack of a rapid, reliable, inexpensive, and treatment-sensitive metrological instrument reflecting feline osteoarthritis (OA) pain. The Montreal Instrument for Cat Arthritis Testing, for Use by Veterinarians (MI-CAT(V)) has been refined in 4 sub-sections, and we proposed its concurrent validation. Cats naturally affected by OA (n = 32) were randomly distributed into 4 groups of firocoxib analgesic (Gr. A: 0.40; B: 0.25; C: 0.15, and P: 0.00 mg/kg bodyweight). They were assessed during Baseline, Treatment, and Recovery periods using MI-CAT(V) and objective outcomes (effort path, stairs assay compliance, and actimetry). The MI-CAT(V) total score correlated to the effort path and actimetry (Rho_S = −0.501 to −0.453; p < 0.001), also being sensitive to treatment responsiveness. The pooled treatment group improved its total, gait, and body posture scores during Treatment compared to the Baseline, Recovery, and placebo group (p < 0.05). The MI-CAT(V) suggested a dose-(especially for Gr. B) and cluster-response. Cats in the moderate and severe MI-CAT(V) clusters responded to firocoxib with a remaining analgesic effect, while the mild cluster seemed less responsive and experienced a negative rebound effect. The MI-CAT(V) was validated for its OA pain severity discriminatory abilities and sensitivity to firocoxib treatment, providing a new perspective for individualized care. Full article

Determining the influence of environmental factors on the stability of drugs is very helpful when choosing excipients, storage conditions or packaging materials. In addition, information about possible toxic degradation products enables detecting and avoiding the harmful side effects of the drug. We used the thin-layer chromatographic-densitometric procedure for the assay of five coxibs, conducted degradation studies in various environments and at different temperatures along with the determination of pharmacokinetic parameters. The results were subjected to chemometric analysis, to investigate and visualize the similarities and differences of the studied coxibs. Samples of the tested drug were also analyzed by UPLC-MS/MS in order to identify degradation products, and determine possible drug degradation pathways. Using the human liver cancer HepG2 cell line, the hepatotoxic effect of the degradation products was also determined. It was observed that all substances were relatively stable under the analyzed conditions and degraded more in acidic than alkaline environments. Robenacoxib is the drug that decomposes the fastest, and cimicoxib turned out to be the most stable. Robenacoxib also showed significant hepatotoxicity at the highest tested concentration, which correlates with the high degree of its degradation, and the probable formation of a more hepatoxic product. The obtained mass spectra of compounds formed as a result of hydrolysis of the protonated drug leading to the formation of several product ions, which enabled us to propose probable degradation pathways. Full article

This systematic review aimed to identify the evidence concerning the analgesic efficacy of non-steroidal anti-inflammatory drugs to treat abdominal pain in horses, and to establish whether one non-steroidal anti-inflammatory drug could provide better analgesia compared to others. This systematic review was conducted following the “Systematic Review Protocol for Animal Intervention Studies”. Research published between 1985 and the end of May 2023 was searched, using three databases, namely, PubMed, Embase, and Scopus, using the words equine OR horse AND colic OR abdominal pain AND non-steroidal anti-inflammatory drug AND meloxicam OR flunixin meglumine OR phenylbutazone OR firocoxib OR ketoprofen. Risk of bias was assessed with the SYRCLE risk of bias tool, and level of evidence scored according to the Oxford Centre for Evidence-based Medicine. A total of 10 studies met the inclusion criteria. From those only one study judged pain with a validated pain score, and a high risk of bias was identified due to the presence of selection, performance, and “other” types of bias. Therefore, caution is required in the interpretation of results from individual studies. To date, the evidence on analgesic efficacy to determine whether one drug is more potent than another regarding the treatment of abdominal pain in horses is sparse. Full article

Firocoxib is a non-steroidal anti-inflammatory drug specifically formulated for veterinary medicine and selectively acts on inhibiting the cyclooxygenase 2 enzyme (COX-2). This study evaluated the possible adverse effects of administering oral therapeutic firocoxib on gastric mucosa, hematological parameters, coagulation cascade, and hepatic and renal biochemistry in healthy horses. Nine clinically healthy Arabian horses, approximately 9 years old, received 0.1 mg/kg of oral firocoxib for 14 days. The gastroscopic examination was conducted 1 day before starting treatment (D0) and two days after the last blood collection (D23). Venous blood samples were obtained for laboratory tests on day 1, immediately prior to the initiation of treatment (D1), after 7 and 14 days of treatment (D7 and D14), and 7 days after the conclusion of treatment (D21. No changes were found in the gastroscopic and hematological tests. Coagulation and serum biochemistry levels remain between these species’ average values. However, the increased activated partial thromboplastin time (aPTT) and prothrombin time (PT) indicate reduced blood coagulation capacity, which contradicts the expected effect of treatment with selective COX-2 inhibitors, as these drugs theoretically promote coagulation. Administering firocoxib to horses is safe as it does not cause significant adverse reactions. Therefore, it is a suitable option for managing inflammatory conditions in these animals with attention to an unexpected adverse anti-coagulopathy effect, and further study is warranted. Full article

This study aimed to investigate the pro-apoptotic effects of NSAID (Previcox^®) in vitro and in vivo. Two CMT cell lines, one from the primary tumor and one from bone metastasis, were treated with firocoxib and MTT assay was performed to determine the half-maximal inhibitory concentration (IC₅₀) value. The firocoxib IC₅₀ for the cell lines UNESP-CM5 and UNESP-MM1 were 25.21 µM and 27.41 µM, respectively. The cell lines were then treated with the respective firocoxib IC₅₀ concentrations and annexin V/propidium iodide (PI) assay was performed, to detect the induction of apoptosis in both cells (Annexin+/PI+). We conducted an in vivo study involving female dogs affected by CMT and divided them into control and treatment groups. For both groups, a biopsy was performed on day 0 (D0) and a mastectomy was performed on day 14 (D14). In the treatment group, after biopsy on D0, the patients received Previcox^® 5 mg/kg PO once a day until mastectomy was performed on D14. COX-2/caspase-3 double immunostaining was performed on samples from D0 and D14, revealing no difference in the control group. In contrast, in the treatment group Previcox^® increased the number of COX-2 positive apoptotic cells. Therefore, firocoxib can induce apoptosis in CMT cells in vitro and in vivo, and Previcox^® can be a potential neoadjuvant treatment for patients with mammary cancer. Full article

Effective pain management in horses can be a challenge despite the understanding that appropriate analgesia improves animal welfare and increases treatment success. The administration of NSAID drugs, particularly phenylbutazone and flunixin, are common practice in equine veterinary patients. Known for their analgesic and anti-inflammatory properties, NSAIDs are used for the treatment of a variety of conditions in horses, from gastrointestinal to orthopedic pain. Despite extensive usage, NSAIDs have a narrow margin of safety and the body of literature documenting the efficacy and side effects of different NSAIDs is broad. The three main side effects associated with excessive or prolonged NSAID usage in horses include gastroduodenal ulceration, right dorsal colitis (RDC) and renal papillary necrosis. The use of cyclooxygenase-2 selective NSAIDS, such as firocoxib, are theoretically safer. The aim of this paper is to review the current literature on the use and efficacy of different NSAIDs, summarise the associated side effects of NSAID usage and evaluate the current state of knowledge for the diagnosis and treatment of such toxicities. Full article

The metrological properties of two performance-based outcome measures of feline osteoarthritis (OA), namely Effort Path (Path) and Stairs Assay Compliance (Stairs), were tested. Cats naturally affected by OA (n = 32) were randomly distributed into four groups (A: 0.40, B: 0.25, C: 0.15, or D: 0.00 mg firocoxib/kg bodyweight) and assessed during baseline, treatment, and recovery periods. For Path, from an elevated walking platform, the cats landed on a pressure-sensitive mattress and jumped up onto a second elevated platform. Analysis included velocity, time to completion, peak vertical force (PVF), and vertical impulse. For Stairs, the number of steps and time to completion were recorded for 16 steps up and down in a 4 min period. Reliability was moderate to very good for Path and poor to good for Stairs. Different normalization methods are described in the manuscript. The placebo group remained stable within-time in Path, whereas treated cats trotted faster on the ramp (p < 0.0001), improved their PVF (p < 0.018) and completed the task quicker (p = 0.003). The percentage of cats completing the Stairs finish line was higher under treatment (p < 0.036), with huge effect size, the placebo group results being stable within-time. Both are promising performance-based outcome measures to better diagnose and manage feline OA pain. Full article

Background: Intestinal ischemic reperfusion (I/R) injury is associated with a high mortality rate; this condition is also related to significant endotoxemia and systemic inflammation. The preservation of tissue perfusion and a sufficient blood flow are required to deliver nutrients and oxygen, preserve metabolic pathways, and eliminate waste products. Oxidative stress plays a fundamental role in intestinal I/R injury and leads to disruption of the mucosal barrier and necrosis, allowing the migration of endotoxins and luminal bacteria into the systemic circulation. In this study, we evaluated the beneficial effects of a cyclooxygenase (COX)-2 inhibitor—firocoxib—plus the antioxidant vitamin C in a rat model of intestinal I/R injury. Methods: We used a rat model of I/R injury in which the superior mesenteric artery was clamped for 30 min by a vascular clamp, and the animals were then allowed 1 h of reperfusion. Results: Our results show the importance of combined anti-inflammatory and antioxidant treatment for the prevention of intestinal I/R injury that leads to reduced systemic endotoxemia. We observed a significantly synergistic effect of firocoxib and vitamin C in reducing intestinal wall damage and oxidative stress, leading to a significant reduction of inflammation and endotoxemia. Conclusions: Our results indicate that this approach could be a new pharmacological protocol for intestinal colic or ischemic injury-induced endotoxemia. Full article

An electrospinning process was optimized to produce fibers of micrometric size with different combinations of polymeric and surfactant materials to promote the dissolution rate of an insoluble drug: firocoxib. Scanning Electron Microscopy (SEM) showed that only some combinations of the proposed carrier systems allowed the production of suitable fibers and further fine optimization of the technique is also needed to load the drug. Differential scanning calorimetry (DSC) and X-ray powder diffraction (XRPD) suggest that the drug is in an amorphous state in the final product. Drug amorphization, the fine dispersion of the active in the carriers, and the large surface area exposed to water interaction obtained through the electrospinning process can explain the remarkable improvement in the dissolution performance of firocoxib from the final product developed. Full article