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1.
Dermatol Online J ; 30(2)2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38959933

RESUMO

Drug-induced pseudoporphyria is commonly linked to nonsteroidal anti-inflammatory drugs (NSAIDs) such as naproxen, oxaprozin, ketoprofen, and ibuprofen. The NSAID meloxicam is not a commonly reported inciting agent. We report a case of meloxicam-induced pseudoporphyria in a 55-year-old woman with a past medical history of hypertension, hyperlipidemia, gastroesophageal reflux disease, and osteoarthritis. She presented to the clinic with tense and denuded bullae on her dorsal feet, which was diagnosed as pseudoporphyria after further workup. Upon evaluating the patient's medication history, meloxicam was identified as the most likely inciting agent. The patient's condition resolved with the discontinuation of this medication. Our findings can help dermatologists effectively diagnose and treat meloxicam-induced pseudoporphyria in patients with similar cases.


Assuntos
Anti-Inflamatórios não Esteroides , Meloxicam , Humanos , Meloxicam/efeitos adversos , Feminino , Pessoa de Meia-Idade , Anti-Inflamatórios não Esteroides/efeitos adversos , Tiazóis/efeitos adversos , Porfirias/induzido quimicamente , Dermatoses do Pé/induzido quimicamente , Dermatoses do Pé/patologia , Tiazinas/efeitos adversos
2.
J Vet Intern Med ; 38(4): 2324-2332, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38944675

RESUMO

BACKGROUND: Grapiprant is a novel anti-inflammatory drug approved for the treatment of pain associated with osteoarthritis in dogs. OBJECTIVE: Compare the efficacy of grapiprant vs meloxicam for the management of postoperative joint pain in dogs. ANIMALS: Forty-eight dogs presented with cranial cruciate ligament disease and treated by tibial plateau leveling osteotomy (TPLO) between May 2020 and May 2022. METHODS: In this randomized, double blinded, prospective clinical trial, client-owned dogs with naturally occurring unilateral cruciate ligament rupture were enrolled on the day of surgery. The day after surgery, all animals received a subcutaneous injection of 0.2 mg/kg of meloxicam and were randomly assigned to receive either oral grapiprant (2 mg/kg) or meloxicam (0.1 mg/kg), once a day for 14 days, in a blinded manner. The primary endpoint of the study was the pain severity (PSS) and interference (PIS) scores, assessed by the Canine Brief Pain Inventory (CBPI) at day 3, 7, 10 and 15 after the surgery. RESULTS: Three days after surgery, grapiprant treated dogs had lower PSS compared to meloxicam treated dogs with a mean ± SD of 2.76 ± 0.18 vs 3.25 ± 0.23, respectively (difference of -0.49 [95% CI -0.94 to -0.04], P = .032). Pain Interference Score was also lower in grapiprant group at day 3 (4.11 ± 0.18 vs 4.69 ± 0.16 in meloxicam group [difference of -0.58 {95% CI -1.03 to -0.13}, P = .013]) and at day 10 (2.23 ± 0.13 vs 2.72 ± 0.28 [difference of -0.49 {95% CI -0.92 to -0.01}, P = .049]). CONCLUSIONS AND CLINICAL IMPORTANCE: Our study supports the use of grapiprant as an alternative analgesic to meloxicam for management of postoperative joint pain in dogs.


Assuntos
Anti-Inflamatórios não Esteroides , Doenças do Cão , Meloxicam , Dor Pós-Operatória , Animais , Cães , Meloxicam/uso terapêutico , Dor Pós-Operatória/veterinária , Dor Pós-Operatória/tratamento farmacológico , Doenças do Cão/tratamento farmacológico , Doenças do Cão/cirurgia , Masculino , Método Duplo-Cego , Feminino , Anti-Inflamatórios não Esteroides/uso terapêutico , Estudos Prospectivos , Lesões do Ligamento Cruzado Anterior/veterinária , Lesões do Ligamento Cruzado Anterior/cirurgia , Piridinas/uso terapêutico , Osteotomia/veterinária , Medição da Dor/veterinária , Benzenossulfonamidas , Imidazóis , Compostos de Sulfonilureia
3.
Clin Transl Sci ; 17(5): e13798, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38700290

RESUMO

Fexuprazan, a novel potassium-competitive acid blocker, is expected to be used for the prevention of nonsteroidal anti-inflammatory drugs (NSAIDs) induced ulcer. This study aimed to evaluate pharmacokinetic (PK) interactions between fexuprazan and NSAIDs in healthy subjects. A randomized, open-label, multicenter, six-sequence, one-way crossover study was conducted in healthy male subjects. Subjects randomly received one of the study drugs (fexuprazan 40 mg BID, celecoxib 200 mg BID, naproxen 500 mg BID, or meloxicam 15 mg QD) for 5 or 7 days in the first period followed by the combination of fexuprazan and one of NSAIDs for the same days and the perpetrator additionally administered for 1-2 days in the second period. Serial blood samples for PK analysis were collected until 48- or 72-h post-dose at steady state. PK parameters including maximum plasma concentration at steady state (Cmax,ss) and area under plasma concentration-time curve over dosing interval at steady state (AUCτ,ss) were compared between monotherapy and combination therapy. The PKs of NSAIDs were not significantly altered by fexuprazan. For fexuprazan, differences in PK parameters (22% in Cmax, 19% in AUCτ,ss) were observed when co-administered with naproxen, but not clinically significant. The geometric mean ratio (90% confidence interval) of combination therapy to monotherapy for Cmax,ss and AUCτ,ss was 1.22 (1.02-1.46) and 1.19 (1.00-1.43), respectively. There were no significant changes in the systemic exposure of fexuprazan by celecoxib and meloxicam. Fexuprazan and NSAIDs did not show clinically meaningful PK interactions.


Assuntos
Anti-Inflamatórios não Esteroides , Estudos Cross-Over , Interações Medicamentosas , Humanos , Masculino , Anti-Inflamatórios não Esteroides/farmacocinética , Anti-Inflamatórios não Esteroides/administração & dosagem , Adulto , Adulto Jovem , Voluntários Saudáveis , Área Sob a Curva , Meloxicam/farmacocinética , Meloxicam/administração & dosagem , Naproxeno/farmacocinética , Naproxeno/administração & dosagem , Celecoxib/farmacocinética , Celecoxib/administração & dosagem , Pessoa de Meia-Idade
4.
J Colloid Interface Sci ; 670: 486-498, 2024 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-38772264

RESUMO

Establishing a physical barrier between the peritoneum and the cecum is an effective method to reduce the risk of postoperative abdominal adhesions. Meloxicam (MX), a nonsteroidal anti-inflammatory drug has also been applied to prevent postoperative adhesions. However, its poor water solubility has led to low bioavailability. Herein, we developed an injectable hydrogel as a barrier and drug carrier for simultaneous postoperative adhesion prevention and treatment. A third-generation polyamide-amine dendrimer (G3) was exploited to dynamically combine with MX to increase the solubility and the bioavailability. The formed G3@MX was further used to crosslink with poly-γ-glutamic acid (γ-PGA) to prepare a hydrogel (GP@MX hydrogel) through the amide bonding. In vitro and in vivo experiments evidenced that the hydrogel had good biosafety and biodegradability. More importantly, the prepared hydrogel could control the release of MX, and the released MX is able to inhibit inflammatory responses and balance the fibrinolytic system in the injury tissues in vivo. The tunable rheological and mechanical properties (compressive moduli: from âˆ¼ 57.31 kPa to âˆ¼ 98.68 kPa;) and high anti-oxidant capacity (total free radical scavenging rate of âˆ¼ 94.56 %), in conjunction with their syringeability and biocompatibility, indicate possible opportunities for the development of advanced hydrogels for postoperative tissue adhesions management.


Assuntos
Dendrímeros , Hidrogéis , Meloxicam , Nylons , Ácido Poliglutâmico , Hidrogéis/química , Hidrogéis/farmacologia , Animais , Ácido Poliglutâmico/química , Ácido Poliglutâmico/farmacologia , Ácido Poliglutâmico/análogos & derivados , Nylons/química , Aderências Teciduais/prevenção & controle , Dendrímeros/química , Dendrímeros/farmacologia , Meloxicam/química , Meloxicam/farmacologia , Meloxicam/administração & dosagem , Camundongos , Inflamação/prevenção & controle , Inflamação/tratamento farmacológico , Anti-Inflamatórios não Esteroides/farmacologia , Anti-Inflamatórios não Esteroides/química , Anti-Inflamatórios não Esteroides/administração & dosagem , Ratos , Ratos Sprague-Dawley , Fibrinólise/efeitos dos fármacos , Complicações Pós-Operatórias/prevenção & controle , Tamanho da Partícula , Injeções , Portadores de Fármacos/química
5.
Inorg Chem ; 63(17): 7613-7618, 2024 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-38632683

RESUMO

Meloxicam (MLX) is a novel nonsteroidal anti-inflammatory drug, but on the other hand, it has become one of the common microcontaminants in surface waters and sewage. Herein, we report the preparation of a ternary-metal Zn(II)-Cd(II)-Eu(III) nanocluster 1 for the response of MLX through the enhancement of lanthanide luminescence. The luminescence sensing behavior of 1 is expressed by the equation I615nm = 3060 × [MLX] + 46,604, which can be used in the quantitative analysis of MLX concentrations in meloxicam dispersible tablets. Filter paper strips bearing 1 can be used to qualitatively detect MLX by a color change to red under a UV lamp. The luminescence response time is no more than five s, and the detection limit is as low as 2.31 × 10-2 nM.


Assuntos
Anti-Inflamatórios não Esteroides , Európio , Meloxicam , Zinco , Meloxicam/análise , Zinco/química , Zinco/análise , Európio/química , Anti-Inflamatórios não Esteroides/análise , Anti-Inflamatórios não Esteroides/química , Medições Luminescentes , Luminescência , Nanoestruturas/química , Limite de Detecção
6.
Crit Rev Ther Drug Carrier Syst ; 41(5): 111-150, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38608134

RESUMO

Meloxicam, a selective COX-2 inhibitor, has demonstrated clinical effectiveness in managing inflammation and acute pain. Although available in oral and parenteral formulations such as capsule, tablet, suspension, and solution, frequent administration is necessary to maintain therapeutic efficacy, which can increase adverse effects and patient non-compliance. To address these issues, several sustained drug delivery strategies such as oral, transdermal, transmucosal, injectable, and implantable drug delivery systems have been developed for meloxicam. These sustained drug delivery strategies have the potential to improve the therapeutic efficacy and safety profile of meloxicam, thereby reducing the frequency of dosing and associated gastrointestinal side effects. The choice of drug delivery system will depend on the desired release profile, the target site of inflammation, and the mode of administration. Overall, meloxicam sustained delivery systems offer better patient compliance, and reduce the side effects, thereby improving the clinical applications of this drug. Herein, we discuss in detail different strategies for sustained delivery of meloxicam.


Assuntos
Dor Aguda , Analgésicos , Humanos , Meloxicam , Sistemas de Liberação de Medicamentos , Inflamação
7.
Int J Pharm ; 655: 124013, 2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38503398

RESUMO

Machine vision systems have emerged for quality assessment of solid dosage forms in the pharmaceutical industry. These can offer a versatile tool for continuous manufacturing while supporting the framework of process analytical technology, quality-by-design, and real-time release testing. The aim of this work is to develop a digital UV/VIS imaging-based system for predicting the in vitro dissolution of meloxicam-containing tablets. The alteration of the dissolution profiles of the samples required different levels of the critical process parameters, including compression force, particle size and content of the API. These process parameters were predicted non-destructively by multivariate analysis of UV/VIS images taken from the tablets. The dissolution profile prediction was also executed using solely the image data and applying artificial neural networks. The prediction error (RMSE) of the dissolution profile points was less than 5%. The alteration of the API content directly affected the maximum concentrations observed at the end of the dissolution tests. This parameter was predicted with a relative error of less than 10% by PLS models that are based on the color components of UV and VIS images. In conclusion, this paper presents a modern, non-destructive PAT solution for real-time testing of the dissolution of tablets.


Assuntos
Indústria Farmacêutica , Redes Neurais de Computação , Meloxicam , Análise Multivariada , Comprimidos , Solubilidade
8.
Pain ; 165(8): 1761-1773, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-38452214

RESUMO

ABSTRACT: The pressing need for safer, more efficacious analgesics is felt worldwide. Preclinical tests in animal models of painful conditions represent one of the earliest checkpoints novel therapeutics must negotiate before consideration for human use. Traditionally, the pain status of laboratory animals has been inferred from evoked nociceptive assays that measure their responses to noxious stimuli. The disconnect between how pain is tested in laboratory animals and how it is experienced by humans may in part explain the shortcomings of current pain medications and highlights a need for refinement. Here, we survey human patients with chronic pain who assert that everyday aspects of life, such as cleaning and leaving the house, are affected by their ongoing level of pain. Accordingly, we test the impact of painful conditions on an ethological behavior of mice, digging. Stable digging behavior was observed over time in naive mice of both sexes. By contrast, deficits in digging were seen after acute knee inflammation. The analgesia conferred by meloxicam and gabapentin was compared in the monosodium iodoacetate knee osteoarthritis model, with meloxicam more effectively ameliorating digging deficits, in line with human patients finding meloxicam more effective. Finally, in a visceral pain model, the decrease in digging behavior correlated with the extent of disease. Ultimately, we make a case for adopting ethological assays, such as digging, in studies of pain in laboratory animals, which we believe to be more representative of the human experience of pain and thus valuable in assessing clinical potential of novel analgesics in animals.


Assuntos
Comportamento Animal , Animais , Camundongos , Humanos , Masculino , Feminino , Comportamento Animal/efeitos dos fármacos , Comportamento Animal/fisiologia , Dor/tratamento farmacológico , Dor/psicologia , Dor/fisiopatologia , Analgésicos/uso terapêutico , Analgésicos/farmacologia , Camundongos Endogâmicos C57BL , Modelos Animais de Doenças , Pessoa de Meia-Idade , Medição da Dor/métodos , Idoso , Dor Crônica/psicologia , Dor Crônica/tratamento farmacológico , Dor Crônica/fisiopatologia , Gabapentina/uso terapêutico , Gabapentina/farmacologia , Adulto , Meloxicam/uso terapêutico
11.
Pharm Res ; 41(4): 673-685, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38472609

RESUMO

PURPOSE: The purpose of this study was to develop a simulation model for the pharmacokinetics (PK) of drugs undergoing enterohepatic circulation (EHC) with consideration to the environment in the gastrointestinal tract in the fed state in humans. The investigation particularly focused on the necessity of compensating for the permeability rate constant in the reabsorption process in consideration of drug entrapment in bile micelles. METHODS: Meloxicam and ezetimibe were used as model drugs. The extent of the entrapment of drugs inside bile micelles was evaluated using the solubility ratio of Fed State Simulated Intestinal Fluid version 2 (FeSSIF-V2) to Fasted State Simulated Intestinal Fluid version 2 (FaSSIF-V2). Prediction accuracy was evaluated using the Mean Absolute Percentage Error (MAPE) value, calculated from the observed and predicted oral PK profiles. RESULTS: The solubilization of ezetimibe by bile micelles was clearly observed while that of meloxicam was not. Assuming that only drugs in the free fraction of micelles permeate through the intestinal membrane, PK simulation for ezetimibe was performed in both scenarios with and without compensation by the permeation rate constant. The MAPE value of Zetia® tablet, containing ezetimibe, was lower with compensation than without compensation. By contrast, Mobic® tablet, containing meloxicam, showed a relatively low MAPE value even without compensation. CONCLUSION: For drugs which undergo EHC and can be solubilized by bile micelles, compensating for the permeation rate constant in the reabsorption process based on the free fraction ratio appears an important factor in increasing the accuracy of PK profile prediction.


Assuntos
Circulação Êntero-Hepática , Micelas , Humanos , Meloxicam , Solubilidade , Ezetimiba , Comprimidos
12.
Small ; 20(28): e2309882, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38342670

RESUMO

Negative therapeutic feedback of inflammation would extensively attenuate the antitumor effect of photodynamic therapy (PDT). In this work, tumor homing chimeric peptide rhomboids (designated as NP-Mel) are fabricated to improve photodynamic performance by inhibiting PDT-upregulated cyclooxygenase-2 (COX-2). The hydrophobic photosensitizer of protoporphyrin IX (PpIX) and palmitic acid are conjugated onto the neuropilin receptors (NRPs) targeting peptide motif (CGNKRTR) to obtain tumor homing chimeric peptide (Palmitic-K(PpIX)CGNKRTR), which can encapsulate the COX-2 inhibitor of meloxicam. The well dispersed NP-Mel not only improves the drug stability and reactive oxygen species (ROS) production ability, but also increase the breast cancer targeted drug delivery to intensify the PDT effect. In vitro and in vivo studies verify that NP-Mel will decrease the secretion of prostaglandin E2 (PGE2) after PDT treatment, inducing the downregulation of IL-6 and TNF-α expressions to suppress PDT induced inflammation. Ultimately, an improved PDT performance of NP-Mel is achieved without inducing obvious systemic toxicity, which might inspire the development of sophisticated nanomedicine in consideration of the feedback induced therapeutic resistance.


Assuntos
Ciclo-Oxigenase 2 , Peptídeos , Fotoquimioterapia , Fotoquimioterapia/métodos , Ciclo-Oxigenase 2/metabolismo , Peptídeos/química , Peptídeos/farmacologia , Animais , Humanos , Linhagem Celular Tumoral , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/química , Espécies Reativas de Oxigênio/metabolismo , Feminino , Meloxicam/farmacologia , Meloxicam/uso terapêutico , Camundongos , Protoporfirinas/química , Protoporfirinas/farmacologia , Dinoprostona/metabolismo
13.
Int J Biol Macromol ; 262(Pt 1): 130015, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38331066

RESUMO

The intranasal administration of drugs using environmentally responsive formulations, employing a combination of hydroxypropyl methylcellulose (HPMC) and poloxamer 407 (P407), can result in release systems that may assist in the treatment of neurological diseases. Meloxicam, considered a potential adjuvant in the treatment of Alzheimer's disease, could be used in these platforms. The aim of this work was to develop a mucoadhesive, thermoresponsive, and nanostructured system containing HPMC for nose-to-brain administration of meloxicam. The initially selected systems were investigated for their rheological, mechanical, and micellar size characteristics. The systems were dilatant at 25 °C and pseudoplastic with a yield value at 37 °C, showing viscoelastic properties at both temperatures. The platform containing HPMC (0.1%, w/w) and P407 (17.5%, w/w) was selected and demonstrated good mucoadhesive properties, along with an appropriate in vitro release profile. HPMC could form a binary system with P407, displaying superior mucoadhesive and thermoresponsive properties for nose-to-brain meloxicam administration, indicating that the selected formulation is worthy of clinical studies.


Assuntos
Encéfalo , Poloxâmero , Administração Intranasal , Derivados da Hipromelose , Meloxicam , Encéfalo/metabolismo , Metilcelulose
14.
Nanomedicine (Lond) ; 19(7): 615-632, 2024 03.
Artigo em Inglês | MEDLINE | ID: mdl-38348578

RESUMO

Background: We aimed to investigate the simultaneous effects of meloxicam and rifampin nanoformulations with solid lipid nanoparticle (SLN) and nanostructured lipid carrier (NLC) substrates on inhibiting the quorum-sensing system of Pseudomonas aeruginosa and preventing biofilm formation by this bacterium. Methods: Antimicrobial activity of rifampin and meloxicam encapsulated with SLNs and NLCs against P. aeruginosa PAO1 was assessed by disk diffusion, minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC). Results: The SLN formulation was associated with lower doses for the MIC and minimum bactericidal concentration in comparison to NLC. Moreover, our results demonstrated that both nanoformulations were able to produce 100% inhibition of the biofilm formation of P. aeruginosa PAO1. Conclusion: All these findings suggest that meloxicam and rifampin encapsulated with SLNs could be the most effective formulation against P. aeruginosa.


Assuntos
Pseudomonas aeruginosa , Percepção de Quorum , Biofilmes , Meloxicam/farmacologia , Rifampina/farmacologia , Antibacterianos/farmacologia
15.
J Vet Med Sci ; 86(4): 374-380, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38325838

RESUMO

This study aimed the efficacy of meloxicam (MX) in treating acute clinical mastitis (ACM) without systemic symptoms in Holstein cows by studying improvement in udder pain, changes in prostaglandin E2(PGE2) and bradykinin (BK) levels in the milk, and milk yield (MY) after healing. Forty-two cows with ACM were randomly assigned to the MX treatment group (T group; n=21) and the control group (C group; n=21). At onset of illness (day 0), the T group received a 0.5 mg/kg subcutaneous (SC) injection of MX whereas the C group received 15 mL SC of saline solution as a placebo. Udder tenderness (UT) was measured, and milk samples were collected on days 0-3. There was little change in the MY of the T group before and after healing, whereas MY in the C group was significantly lower than after healing. UT on day 3 in the T group was significantly lower than that in the C group. PGE2 levels significantly decreased from day 0 to day 3 in both groups. A significant negative correlation between PGE2 and linear score was observed on day 1 in the T group, but not in the C group. In ACM without systemic symptoms, the administration MX may be useful for restoring MY and reducing udder pain after healing.


Assuntos
Doenças dos Bovinos , Mastite Bovina , Feminino , Bovinos , Animais , Meloxicam/uso terapêutico , Meloxicam/farmacologia , Leite , Dor/veterinária , Mastite Bovina/tratamento farmacológico , Glândulas Mamárias Animais , Lactação , Contagem de Células/veterinária , Doenças dos Bovinos/tratamento farmacológico
16.
Res Vet Sci ; 169: 105179, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38335894

RESUMO

Ovariohysterectomy (OVH) is a widely used surgical procedure in small animal practice. In developing countries, injectable anesthetics such as ketamine and xylazine are commonly used in veterinary medicine. Pharmacological agents with analgesic activity, such as ketamine and meloxicam, are not sufficiently effective in reducing visceral pain. Therefore, this study aimed to investigate the visceral analgesia and anti-inflammatory effectiveness of maropitant compared with those of meloxicam during and after OVH in bitches. In this study, thirty-six bitches were randomly divided into the maropitant, meloxicam, and control groups. The heart rate (HR), peripheral oxygen saturation, and respiratory rate were monitored during the procedure. Pain scores were assessed using the University of Melbourne pain scale (UMPS). Rescue analgesia was not necessary for any bitch at any time point. Blood samples were collected before anesthesia induction and 24 h after the operation to determine C-reactive protein (CRP) levels. No significant difference was observed in HR between the control and meloxicam groups when the right ovary was removed, and the HR of the maropitant group was significantly (p < 0.05) lower than that of the control group. The pain scores of the maropitant group were significantly (p < 0.05) lower than those of the other groups. However, no significant differences were observed in CRP levels between the groups. In conclusion, compared to meloxicam, maropitant provided more effective visceral analgesia in bitches undergoing OVH, although no significant difference was found in its anti-inflammatory effect.


Assuntos
Analgesia , Doenças do Cão , Ketamina , Quinuclidinas , Feminino , Cães , Animais , Meloxicam/uso terapêutico , Manejo da Dor/veterinária , Ovariectomia/efeitos adversos , Ovariectomia/veterinária , Dor Pós-Operatória/tratamento farmacológico , Dor Pós-Operatória/prevenção & controle , Dor Pós-Operatória/veterinária , Histerectomia/veterinária , Analgesia/veterinária , Anti-Inflamatórios/uso terapêutico
17.
J Am Vet Med Assoc ; 262(4): 498-505, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38190805

RESUMO

OBJECTIVE: This study sought to determine whether firocoxib (FIRO) or meloxicam (MEL) was effective at providing analgesia after surgical castration in goats. ANIMALS: 18 intact male crossbred goats (6 to 8 months old) were enrolled with a mean weight of 32.6 (± 2.9) kg. METHODS: Surgical castration was done under injectable anesthesia by a licensed veterinarian. Twelve bucks were surgically castrated and given either FIRO (n = 6) or MEL (n = 6). Six bucks served as controls (CNTLs) and were not castrated. Outcome measurements included visual analogue scale, infrared thermography, plasma cortisol, plasma substance P, and kinetic gait analysis. All outcome measurements were obtained at -24, 4, 8, 24, 48, and 72 hours. RESULTS: All 3 treatments were significantly different from each other at the 24- and 48-hour time points, with MEL animals having lower visual analogue scale scores when compared to FIRO animals; CNTL animals exhibited the lowest plasma cortisol levels (3.19 ng/mL; 95% CI, -1.21 to 7.59 ng/mL) followed by FIRO (7.45 ng/mL; 95% CI, 3.10 to 11.80 ng/mL) and MEL (10.24 ng/mL; 95% CI, 5.87 to 14.60 ng/mL). FIRO had an average mean decrease in gait velocity change (-54.17 cm/s; 95% CI, -92.99 to -15.35 cm/s), while MEL had an increase in gait velocity when compared to baseline values (14.54 cm/s; 95% CI, -24.27 to 53.36 cm/s). Control animals had an average mean of -3.06 cm/s (95% CI, -41.88 to 35.75 cm/s). CLINICAL RELEVANCE: Results from this study showed that there were some analgesic effects from administering MEL when compared to bucks that received a placebo treatment (CNTL).


Assuntos
4-Butirolactona/análogos & derivados , Anti-Inflamatórios não Esteroides , Sulfonas , Tiazinas , Masculino , Animais , Meloxicam/uso terapêutico , Anti-Inflamatórios não Esteroides/uso terapêutico , Hidrocortisona , Cabras , Tiazinas/uso terapêutico , Tiazóis/uso terapêutico , Orquiectomia/veterinária , Orquiectomia/métodos , Dor/veterinária
18.
J Vet Pharmacol Ther ; 47(3): 175-186, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38235901

RESUMO

We evaluated the effect of administration timing of meloxicam and robenacoxib on renal function, platelet cyclo-oxygenase and perioperative analgesia in 60 cats undergoing ovariohysterectomy, in a prospective randomized blinded controlled study. Twelve cats were randomly allocated to one subcutaneous treatment group: meloxicam (0.2 mg/kg) or robenacoxib (2 mg/kg) at admission (MA, RA), at induction (MI, RI) and robenacoxib at the end of surgery (RE). All cats received the same anaesthesia protocol. Plasma renin activity (PRA), plasma creatinine, drug concentrations and serum thromboxane (TxB2) were measured sequentially. Anaesthesia significantly increased PRA, as activity at end of the surgery was higher than 2 h later (mean ± SD: 26.6 ± 2.8 versus 10.0 ± 3.9 ng/mL/h). PRA remained higher at 2 h post-surgery in admission groups compared to induction groups (p = .01). Serum TxB2 was lower with meloxicam than robenacoxib (p = .001), and was lower in the MA than each robenacoxib group at catheter placement. Admission groups (16/24 from RA and MA groups) received earlier rescue analgesia than other groups (p = .033). In conclusion, the renin-angiotensin system was activated during anaesthesia despite cyclo-oxygenase inhibition, possibly due to hypotension or surgical stimulation. There was no effect of drug or timing on the markers of renal function but one cat receiving meloxicam at induction had suspected IRIS grade II acute kidney injury.


Assuntos
Difenilamina , Histerectomia , Meloxicam , Ovariectomia , Dor Pós-Operatória , Fenilacetatos , Animais , Gatos , Feminino , Analgesia/veterinária , Analgesia/métodos , Anti-Inflamatórios não Esteroides/administração & dosagem , Anti-Inflamatórios não Esteroides/farmacologia , Anti-Inflamatórios não Esteroides/uso terapêutico , Difenilamina/farmacologia , Difenilamina/administração & dosagem , Difenilamina/análogos & derivados , Histerectomia/veterinária , Rim/efeitos dos fármacos , Meloxicam/administração & dosagem , Meloxicam/farmacologia , Meloxicam/uso terapêutico , Ovariectomia/veterinária , Dor Pós-Operatória/veterinária , Dor Pós-Operatória/tratamento farmacológico , Dor Pós-Operatória/prevenção & controle , Fenilacetatos/administração & dosagem , Fenilacetatos/farmacologia
19.
Sci Rep ; 14(1): 1893, 2024 01 22.
Artigo em Inglês | MEDLINE | ID: mdl-38253707

RESUMO

This study presents two spectrophotometric methods; a novel dual wavelength-derivative spectrophotometry and multivariate curve resolution-alternating least squares (MCR-ALS) for the simultaneous determination of a fixed dose combination of bupivacaine (BUP) and meloxicam (MEL) in a ratio of 30:1. The extended UV spectrum of MEL enables its direct determination at λmax 360 nm with no interference from BUP. The determination of BUP was unfeasible directly because the UV spectra of both drugs are moderately overlapped over the wavelength range of 250-450 nm, thus new chemometric based spectrophotometric methods should be developed for its determination. Dual wavelength-derivative method was employed based on using first derivative spectra. The selected dual wavelengths for determination BUP were 274.6 nm and 374.6 nm where the dA/dλ amplitudes differences for MET are equal to zero. MCR-ALS is advanced chemometric tool that enables analysis of multicomponent samples in complex matrices with high resolution based on the decomposition of signal/spectral data into the pure spectra and corresponding concentration profile. The figures of merits for MCR model show that there is a good agreement between the actual and predicted concentrations for MEL and BUP. The methods were validated and statistically compared with a reported HPLC method.


Assuntos
Bupivacaína , Quimiometria , Meloxicam , Cromatografia Líquida de Alta Pressão , Espectrofotometria
20.
PLoS One ; 19(1): e0294720, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38227583

RESUMO

Usage and reporting of analgesia in animal models of spinal cord injury (SCI) have been sparse and requires proper attention. The majority of experimental SCI research uses rats as an animal model. This study aimed to probe into the effects of some commonly used regimens with NSAIDs and opioids on well-being of the rats as well as on the functional outcome of the model. This eight-week study used forty-two female Wistar rats (Crl: WI), randomly and equally divided into 6 treatment groups, viz. I) tramadol (5mg/kg) and buprenorphine (0.05mg/kg); II) carprofen (5mg/kg) and buprenorphine (0.05mg/kg); III) carprofen (5mg/kg); IV) meloxicam (1mg/kg) and buprenorphine (0.05mg/kg); V) meloxicam (1mg/kg); and VI) no analgesia (0.5 ml sterile saline). Buprenorphine was administered twice daily whereas other treatments were given once daily for five days post-operatively. Injections were given subcutaneously. All animals underwent dental burr-assisted laminectomy at the T10-T11 vertebra level. A custom-built calibrated spring-loaded 200 kilodynes force deliverer was used to induce severe SCI. Weekly body weight scores, Rat Grimace Scale (RGS), and dark-phase home cage activity were used as markers for well-being. Weekly Basso Beattie and Bresnahan (BBB) scores served as markers for functionality together with Novel Object Recognition test (NOR) at week 8 and terminal histopathology using area of vacuolisation and live neuronal count from the ventral horns of spinal cord. It was concluded that the usage of analgesia improved animal wellbeing while having no effects on the functional aspects of the animal model in comparison to the animals that received no analgesics.


Assuntos
Buprenorfina , Traumatismos da Medula Espinal , Ratos , Feminino , Animais , Laminectomia , Meloxicam , Ratos Wistar , Modelos Animais de Doenças , Traumatismos da Medula Espinal/tratamento farmacológico , Traumatismos da Medula Espinal/cirurgia , Traumatismos da Medula Espinal/patologia , Analgésicos , Medula Espinal/patologia , Buprenorfina/farmacologia , Buprenorfina/uso terapêutico
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