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4.
Ann Hepatol ; 16(5): 818-821, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28809737

RESUMO

Drug induced liver injury is a common cause of acute liver failure (ALF). While most of these cases are due to dose dependent hepatotoxicity with acetaminophen, idiosyncratic drug-induced liver injury (DILI) is responsible for about 15% cases of ALF. Antibiotics are the most common cause of idiosyncratic DILI as well as DILI induced ALF. Etodolac is a selective cycloxygenase- 2 (COX -2) inhibitor non-steroidal anti-inflammatory drug used as an analgesic and anti-inflammatory in musculoskeletal diseases. Severe liver impairment is extremely rare. Till date, only 3 cases of ALF related to etodolac have been reported in the literature. Here we report two cases with a unique presentation of ALF occurring due to DILI caused by etodolac, as diagnosed by Roussel Uclaf Causality Assessment Method (RUCAM).


Assuntos
Doença Hepática Induzida por Substâncias e Drogas/etiologia , Inibidores de Ciclo-Oxigenase 2/efeitos adversos , Etodolac/efeitos adversos , Falência Hepática Aguda/induzido quimicamente , Adulto , Idoso de 80 Anos ou mais , Doença Hepática Induzida por Substâncias e Drogas/diagnóstico , Doença Hepática Induzida por Substâncias e Drogas/terapia , Progressão da Doença , Evolução Fatal , Feminino , Encefalopatia Hepática/induzido quimicamente , Humanos , Falência Hepática Aguda/diagnóstico , Falência Hepática Aguda/terapia , Testes de Função Hepática , Fatores de Risco
5.
Int J Pharm ; 495(2): 913-23, 2015 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-26456294

RESUMO

In this paper, we report an ionic liquid-in-water (IL/w) microemulsion (ME) formulation which is able to solubilize etodolac (ETO), a poorly water soluble drug for topical delivery using BMIMPF6 (1-butyl-3-methylimidazolium hexafluorophosphate) as IL, Tween 80 as surfactant and ethanol as co-surfactant. The prepared ME was characterized for physicochemical parameters, subjected to ex-vivo permeation studies as well as in-vivo pharmacodynamic evaluation. The ex-vivo drug permeation studies through rat skin was performed using Franz-diffusion cell and the IL/w based ME showed maximum mean cumulative percent permeation of 99.030±0.921% in comparison to oil-in-water (o/w) ME (61.548±1.875%) and oily solution (48.830±2.488%) of ETO. In-vivo anti-arthritic and anti-inflammatory activities of the prepared formulations were evaluated using different rodent models and the results revealed that ETO loaded IL/w based ME was found to be more effective in controlling inflammation than oily solution, o/w ME and marketed formulation of ETO. Histopathological studies also demonstrated that IL/w based ME caused no anatomical and pathological changes in the skin.


Assuntos
Portadores de Fármacos/química , Etodolac/administração & dosagem , Etodolac/farmacologia , Imidazóis/química , Líquidos Iônicos/administração & dosagem , Absorção Cutânea , Água/química , Administração Cutânea , Animais , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/efeitos adversos , Anti-Inflamatórios/farmacocinética , Anti-Inflamatórios/farmacologia , Portadores de Fármacos/administração & dosagem , Estabilidade de Medicamentos , Emulsões/administração & dosagem , Emulsões/química , Etodolac/efeitos adversos , Etodolac/farmacocinética , Imidazóis/administração & dosagem , Técnicas In Vitro , Líquidos Iônicos/química , Masculino , Permeabilidade , Ratos , Reologia , Solubilidade
8.
Tohoku J Exp Med ; 231(1): 29-36, 2013 09.
Artigo em Inglês | MEDLINE | ID: mdl-24005244

RESUMO

Non-steroidal anti-inflammatory drugs (NSAIDs) can cause dyspeptic symptoms, including abdominal pain. Gastric mucus is important as the first line of defense against luminal irritants. In the present study, we investigated whether gastric mucus secretion could influence the severity of gastric mucosal injuries or NSAID-induced dyspeptic symptoms. Fifteen Helicobacter pylori-negative, healthy males were administered two types of NSAIDs, a non-selective cyclooxygenase inhibitor, naproxen (300 mg, twice a day), or a cyclooxygenase-2-selective inhibitor, etodolac (200 mg, twice a day), for 1 week in a crossover study, with an interval of ≥ 4 weeks. Study participants underwent endoscopic examinations before and after treatment. Pentagastrin-stimulated gastric secretions were collected for 10 min during endoscopic examinations, and were analyzed for gastric acid levels (mEq/10 min) and mucus output (mg hexose/10 min). The grade of gastric mucosal injury was assessed endoscopically. Among 29 subjects who completed the crossover study, 11 individuals reported abdominal pain following the administration of naproxen or etodolac for 1 week, as judged by elevated pain scores, while 18 individuals did not report abdominal pain. The occurrence of symptoms was not associated with the type of NSAIDs administered or the occurrence of erosive injury visualized by endoscopy. Gastric mucus secretion was significantly increased in subjects without drug-induced abdominal pain (P < 0.05), whereas it was significantly reduced in those with drug-induced abdominal pain (P < 0.05). In conclusion, the occurrence of NSAID-induced abdominal pain is associated with reduced levels of gastric mucus secretion rather than the occurrence of endoscopic mucosal injury.


Assuntos
Dor Abdominal/induzido quimicamente , Anti-Inflamatórios não Esteroides/efeitos adversos , Mucosa Gástrica/metabolismo , Muco/metabolismo , Dor Abdominal/patologia , Adulto , Anti-Inflamatórios não Esteroides/administração & dosagem , Dinoprostona/metabolismo , Etodolac/administração & dosagem , Etodolac/efeitos adversos , Humanos , Masculino , Muco/efeitos dos fármacos , Naproxeno/administração & dosagem , Naproxeno/efeitos adversos , Estômago/efeitos dos fármacos , Adulto Jovem
9.
Pain Pract ; 13(3): 191-7, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22730906

RESUMO

AIM: We aimed to determine the efficacy and safety of etodolac, in acute migraine attacks in comparison with paracetamol (acetaminophen). METHODS: We designed a randomized, double-blind, crossover phase III clinical trial for patients diagnosed with migraine for at least 1 year, according to ICHD-II criteria. Two hundred and twenty-nine adult patients having 2 to 8 attacks monthly from 17 centers were included. The patients were instructed to use 3 attack treatment packages consisting of 1,000 mg paracetamol, 400 mg etodolac, and 800 mg etodolac on 3 migraine attacks of moderate-severe intensity each in a 3-month treatment period, interchangeably. RESULTS: Any pain medication was used in 1,570 migraine attacks while study treatments were used in 1,047 attacks. The results for 1,000 mg paracetamol, 400 mg etodolac, and 800 mg etodolac were as follows: response of headache at 2 hours 44.9%, 48.3% and 46.1%; pain-free at 2 hours 19.2%, 19.3% and 24.1%; sustained pain-free from 2 to 24 hours 34.3%, 38.3% and 41.1%; relapse rates in 2 to 24 hours 7.3%, 14.3% and 9.7%. There were no statistically significant differences between the groups regarding the headache response, pain-free, sustained pain-free, and relapse rates. Nausea, vomiting, phonophobia, or photophobia decreased similarly in all groups within 24 hours of treatment administration. Drug-related adverse events were noted in 8 patients with 1,000 mg paracetamol, in 9 patients with 400 mg etodolac and in 9 patients for 800 mg etodolac during the study. COMMENT: Our study showed that etodolac is a safe and effective alternative in acute migraine treatment and showed comparable efficacy to paracetamol 1,000 mg. Etodolac may be considered as an alternative option for acute treatment of migraine.


Assuntos
Acetaminofen/administração & dosagem , Analgésicos/administração & dosagem , Etodolac/administração & dosagem , Transtornos de Enxaqueca/tratamento farmacológico , Acetaminofen/efeitos adversos , Adolescente , Adulto , Idoso , Analgésicos/efeitos adversos , Estudos Cross-Over , Método Duplo-Cego , Etodolac/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Adulto Jovem
14.
Biol Pharm Bull ; 34(5): 655-9, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21532152

RESUMO

The anti-inflammatory agent etodolac is used worldwide and it has a good gastrointestinal safety profile. Etodolac consists of two enantiomers, S- and R-etodolac. Here, we investigated the beneficial activities of racemic etodolac and its enantiomers. First, we compared S- and R-etodolac in terms of their inhibition of cyclooxygenase (COX) activity in vitro and their suppression of paw swelling in adjuvant-induced arthritic rats. The COX-2 inhibitory and anti-inflammatory effects of etodolac were found to be due to the S-enantiomer. We previously reported that etodolac attenuates allodynia in a mouse model of neuropathic pain by a COX-2-independent mechanism [N. Inoue et al., J. Pharmacol. Sci., 109, 600-605 (2009)]. In the present study, we showed that the anti-allodynic effects of etodolac in mice were also due to the S-enantiomer. In addition, we investigated the ulcerogenic activity of racemic etodolac and its enantiomers. At high doses, racemic etodolac showed a lower gastric lesion index in rats than the equivalent dose of S-etodolac. In contrast, R-etodolac showed no ulcerogenic activity and even showed protection against HCl/ethanol-induced gastric damage in rats. In conclusion, S-etodolac exhibited anti-inflammatory effects mediated by COX-2 inhibition and anti-allodynic effects that were independent of COX-2 inhibition, while R-etodolac showed gastroprotective effects that may contribute to the low gastrointestinal toxicity of racemic etodolac. Our results show that each enantiomer plays a different role in the efficacy and gastrointestinal safety of etodolac.


Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Etodolac/farmacologia , Trato Gastrointestinal/efeitos dos fármacos , Animais , Anti-Inflamatórios não Esteroides/efeitos adversos , Anti-Inflamatórios não Esteroides/química , Etodolac/efeitos adversos , Etodolac/química , Masculino , Camundongos , Ratos , Estereoisomerismo
15.
Int J Clin Pharmacol Ther ; 48(7): 429-34, 2010 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-20557835

RESUMO

OBJECTIVE: To compare the efficacy and safety of S-etodolac with etodolac in the treatment of osteoarthritis in Indian patients. MATERIALS AND METHODS: This was a double-blind, multicentric, comparative clinical trial conducted in 108 Indian patients with osteoarthritis. All patients received either S-etodolac ER 300 mg or etodolac ER 600 mg tablets once daily. Assessment was done on the basis of WOMAC score and VAS pain score, patient's and physician's global assessment of the arthritic condition. All patients were evaluated after every 2 weeks for 4 weeks for efficacy and safety variables. RESULTS AND DISCUSSION: Total 49 patients in the test group and 52 patients in the reference group completed the study. There was significant improvement (p < 0.0001) in all WOMAC subscales (pain, stiffness and physical function), WOMAC total score and VAS pain score in both the groups. Patient's and physician's global assessment of the arthritic condition also improved significantly (p < 0.0001). All patients showed improvement in WOMAC and VAS pain score by (3) 20%. There was no significant difference between the groups for the efficacy parameters. The adverse events reported were few and no serious adverse events were reported. Total 5 patients in S-etodolac group and 2 patients in etodolac group dropped out of the study. Only 1 patient dropped out because of the side effects of burning sensation, palpitations and anxiety in the test group. CONCLUSION: The present study has established the efficacy, tolerability and safety of S-etodolac extended release tablets in the treatment of osteoarthritis in Indian patients.


Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Etodolac/uso terapêutico , Osteoartrite/tratamento farmacológico , Adulto , Idoso , Método Duplo-Cego , Etodolac/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Medição da Dor
16.
Cochrane Database Syst Rev ; (3): CD007357, 2009 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-19588426

RESUMO

BACKGROUND: Etodolac is a selective cyclo-oxygenase-2 (COX-2) inhibitor, with evidence of efficacy in osteoarthritis and rheumatoid arthritis. Its analgesic efficacy in postoperative pain has not been clearly established. There are no systematic reviews on Etodolac's use in this condition. OBJECTIVES: To assess the analgesic efficacy of etodolac in single oral doses for moderate and severe postoperative pain. SEARCH STRATEGY: We searched Cochrane CENTRAL, MEDLINE, EMBASE and the Oxford Pain Relief Database for studies to May 2009. SELECTION CRITERIA: Randomised, double blind, placebo-controlled trials of single dose orally administered etodolac (any formulation) in adults with moderate to severe acute postoperative pain. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trial quality and extracted data. Pain relief or pain intensity data were extracted and converted into the dichotomous outcome of number of participants with at least 50% pain relief over 4 to 6 hours, from which relative risk (RR) and number needed to treat to benefit (NNT) were calculated. Numbers of participants using rescue medication over specified time periods, and time to use of rescue medication, were sought as additional measures of efficacy. Information on adverse events and withdrawals were collected. MAIN RESULTS: Nine studies (1459 participants) compared etodolac and placebo. Studies were of adequate reporting quality, and the majority of participants had pain following dental extractions. The dose of etodolac used was 25 mg to 1200 mg, with most of the information for 100 mg and 200 mg. For at least 50% pain relief over 4 to 6 hours compared with placebo the NNT for etodolac 100 mg (498 participants) was 4.8 (3.5 to 7.8) and for etodolac 200 mg (670 participants) it was 3.3 (2.7 to 4.2). Very limited information with the extended release formulation did not suggest improved benefit for this outcome.The proportion of participants with at least 50% pain relief was 41% with 100 mg and 44% with 200 mg. Remedication was needed by about 60% with etodolac 200 mg or 400 mg over 6 to 8 hours, compared with almost 80% with placebo.Adverse events were uncommon, and not significantly different form placebo. AUTHORS' CONCLUSIONS: Etodolac 200 mg may be a useful analgesic in postoperative pain, with efficacy similar to paracetamol 1000 mg and celecoxib 200 mg. Higher doses may provide analgesia equivalent to more commonly used drugs, such as ibuprofen 400 mg, naproxen 500 mg and diclofenac 50 mg.


Assuntos
Anti-Inflamatórios não Esteroides/administração & dosagem , Inibidores de Ciclo-Oxigenase 2/administração & dosagem , Etodolac/administração & dosagem , Dor Pós-Operatória/tratamento farmacológico , Doença Aguda , Administração Oral , Adulto , Anti-Inflamatórios não Esteroides/efeitos adversos , Inibidores de Ciclo-Oxigenase 2/efeitos adversos , Etodolac/efeitos adversos , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Extração Dentária/efeitos adversos
17.
AAPS PharmSciTech ; 10(3): 724-31, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19479384

RESUMO

Rectal etodolac-Poloxamer gel systems composed of Poloxamer and bioadhesive polymers were developed and evaluated. Hydroxypropylmethyl cellulose, poly)vinyl) pyrrolidone, methyl cellulose, hydroxyethylcellulose, and carbopol were examined as mucoadhesive polymers. The characteristics of the rectal gels differed according to the properties of mucoadhesive polymers. The physicochemical properties such as gelation temperature, gel strength, and bioadhesive force of various formulations were investigated. The analysis of release mechanism showed that the release of etodolac was proportional to the square root of time, indicating that etodolac might be released from the suppositories by Fickian diffusion. The anti-inflammatory effect of etodolac-Poloxamer gel system was also studied in rats. Moreover, liquid suppository of etodolac did not cause any morphological damage to the rectal tissues. These results suggested that in situ gelling liquid suppository with etodolac and mucoadhesive polymer was a physically safe, convenient, and effective rectal dosage form for etodolac.


Assuntos
Anti-Inflamatórios não Esteroides/administração & dosagem , Anti-Inflamatórios não Esteroides/química , Etodolac/administração & dosagem , Etodolac/química , Adesividade , Administração Retal , Algoritmos , Animais , Anti-Inflamatórios não Esteroides/efeitos adversos , Sobrevivência Celular/efeitos dos fármacos , Química Farmacêutica , Etodolac/efeitos adversos , Excipientes/química , Géis , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/patologia , Irritantes , Masculino , Poloxâmero/química , Ratos , Ratos Sprague-Dawley , Reto/patologia , Supositórios , Temperatura
18.
Exp Toxicol Pathol ; 61(4): 371-80, 2009 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-19081232

RESUMO

A single intravenous injection of alloxan, a non-genotoxic diabetogenic chemical, induces proliferative changes in forestomach mucosa of rats, and some lesions progress to squamous cell carcinoma accompanied with inflammatory change. The present study was conducted to examine the effects of a selective cyclooxygenase-2 (COX-2) inhibitor, etodolac, on the proliferative changes of forestomach mucosa in alloxan-induced diabetic rats. Alloxan-induced diabetic rats were fed a diet containing 0.01% etodolac (AL+Et group) and standard diet (AL group). They were sacrificed after 25 and 50 weeks of feeding, respectively. Squamous cell hyperplasia of forestomach was completely suppressed by etodolac after 25 weeks. After 50 weeks of treatment, the proliferative changes in forestomach developed in all rats of the AL+Et group, but in only 55.6% of the rats in the AL group. The severity of proliferative lesions was much enhanced in the AL+Et group compared to the AL group, and was parallel to the inflammatory changes in individual cases. Ulceration and erosion were more severe in the AL+Et group. These findings demonstrate that etodolac suppresses proliferative and inflammatory changes with COX-2 expression of forestomach in the early stage, but enhances them after 50 weeks.


Assuntos
Proliferação de Células/efeitos dos fármacos , Inibidores de Ciclo-Oxigenase 2/farmacologia , Diabetes Mellitus Experimental/patologia , Etodolac/farmacologia , Mucosa Gástrica/efeitos dos fármacos , Aloxano , Animais , Inibidores de Ciclo-Oxigenase 2/administração & dosagem , Inibidores de Ciclo-Oxigenase 2/efeitos adversos , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/enzimologia , Relação Dose-Resposta a Droga , Etodolac/administração & dosagem , Etodolac/efeitos adversos , Feminino , Mucosa Gástrica/enzimologia , Mucosa Gástrica/patologia , Ratos , Ratos Endogâmicos F344 , Neoplasias Gástricas/enzimologia , Neoplasias Gástricas/etiologia , Neoplasias Gástricas/prevenção & controle , Fatores de Tempo
19.
Yonsei Med J ; 49(5): 742-7, 2008 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-18972594

RESUMO

PURPOSE: Non-steroidal anti-inflammatory drugs (NSAID) are frequently used in oral surgical procedures in dentistry. The evaluation of the frequency of sister chromatid exchange (SCE) is accepted as a reliable cytogenetic method to assess the genotoxic effects of environmental factors. MATERIALS AND METHODS: In this study, the genotoxic effects of various NSAIDs were assessed in 30 patients to who they were administered following encluosed third molar surgery using SCE analysis before and after the operation. The frequency of SCE was evaluated before the operation and after 3 days of etodolac, nimesulid and naproxen use. RESULTS: There was no statistically significant difference in the frequency of SCE between the preoperative and postoperative states in patients given etodolac, nimesulid or naproxen sodium. CONCLUSION: Short term use of selective and non-selective NSAIDs was not associated with a significant genotoxic effect that could be detected using the SCE method in peripheric lymphocytes.


Assuntos
Anti-Inflamatórios não Esteroides/efeitos adversos , Dente Serotino/cirurgia , Troca de Cromátide Irmã/efeitos dos fármacos , Adulto , Etodolac/efeitos adversos , Feminino , Humanos , Masculino , Testes de Mutagenicidade , Naproxeno/efeitos adversos , Estudos Prospectivos , Sulfonamidas/efeitos adversos
20.
J Cardiovasc Pharmacol Ther ; 13(4): 252-60, 2008 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-18787084

RESUMO

BACKGROUND: This study compares the risk of acute myocardial infarction among patients exposed to etodolac, naproxen, celecoxib, and rofecoxib. METHODS: A retrospective cohort study in 38 258 veteran patients (26 376 patient-years) measured the adjusted odds ratios of acute myocardial infarction during exposure to etodolac, naproxen, celecoxib, or rofecoxib. RESULTS: Diagnosis of acute myocardial infarction was confirmed in 100 patients who were exposed to a study nonsteroidal anti-inflammatory drug. Compared to naproxen, the increased risk of acute myocardial infarction was not significant for etodolac (OR = 1.32, P = .27), whereas celecoxib (OR = 2.18, 95% CI 1.09-4.35, P = .03) and rofecoxib (OR = 2.16, 95 CI 1.04-4.46, P = .04) were significant. A post hoc analysis indicates that patients with a prior history of acute myocardial infarction had a significant, 4.26-fold risk for another acute myocardial infarction if taking celecoxib or rofecoxib. CONCLUSION: Etodolac is not associated with a statistically increased risk of acute myocardial infarction compared to naproxen.


Assuntos
Inibidores de Ciclo-Oxigenase 2/efeitos adversos , Etodolac/efeitos adversos , Infarto do Miocárdio/induzido quimicamente , Naproxeno/efeitos adversos , Idoso , Anti-Inflamatórios não Esteroides/efeitos adversos , Celecoxib , Estudos de Coortes , Revisão de Uso de Medicamentos/estatística & dados numéricos , Medicamentos Genéricos/efeitos adversos , Humanos , Incidência , Lactonas/efeitos adversos , Masculino , Prontuários Médicos/estatística & dados numéricos , Pessoa de Meia-Idade , Infarto do Miocárdio/diagnóstico , Infarto do Miocárdio/epidemiologia , Prevalência , Prognóstico , Pirazóis/efeitos adversos , Estudos Retrospectivos , Medição de Risco/métodos , Fatores de Risco , Sulfonamidas/efeitos adversos , Sulfonas/efeitos adversos , Texas/epidemiologia , Veteranos/estatística & dados numéricos
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