RESUMEN
Tolmetin sodium (TS) is a nonsteroidal anti-inflammatory drug (NSAID) indicated for treatment of musculoskeletal issues. As other NSAID, TS displays a marked side effects on the gastro-intestinal (GI) tract after oral administration. Traditional solid suppositories can cause pain and discomfort for patients, may reach the end of the colon; consequently, the drug can undergo the first-pass effect. TS liquid suppository (TS-LS) was developed to enhance patient compliance and rectal mucosal safety in high-risk patients receiving highly NSAID therapy. This work was conducted to optimize and evaluate Poloxamer P407/P188-based thermoresponsive TS-LS by using mucoadhesive polymers such as methylcellulose (MC). TS-LS was prepared by cold method and characterized their in vitro physicochemical properties as gelation temperature (GT), gel strength, bioadhesive properties, and in vitro release. The safety of the prepared suppository on rectum, stomach, and liver was evaluated histologically. Pharmacokinetic analyses were performed to compare rectal TS-LS to orally Rhumtol® capsules. The results showed that the optimized TS-LS; composed of P407/P188/MC (21/9/0.5% w/w) displayed gelation at rectum temperature â¼32.90 °C, gel strength of 21.35 s and rectal retention force at the administration site of 24.25 × 102 dyne/cm2. Moreover, TS-LS did not cause any morphological damage to the rectal tissues. Pharmacokinetic parameters of optimized TS-LS formulation revealed 4.6 fold increase in bioavailability as compared to Rhumtol® capsules. Taken together, the results demonstrated that liquid suppository is a potential and physically safe rectal delivery carrier for improvement rectal bioavailability and in vivo safety of TS.
Asunto(s)
Antiinflamatorios no Esteroideos/administración & dosificación , Tolmetina/administración & dosificación , Administración Oral , Administración Rectal , Animales , Antiinflamatorios no Esteroideos/farmacocinética , Antiinflamatorios no Esteroideos/toxicidad , Disponibilidad Biológica , Cápsulas , Enfermedad Hepática Inducida por Sustancias y Drogas/metabolismo , Composición de Medicamentos , Geles , Humanos , Masculino , Poloxámero , Conejos , Ratas Sprague-Dawley , Supositorios , Temperatura , Adhesivos Tisulares , Tolmetina/farmacocinética , Tolmetina/toxicidadRESUMEN
Glucuronidation, an important phase II metabolic route, is generally considered to be a detoxification pathway. However, acyl glucuronides (AGs) have been implicated in the toxicity of carboxylic acid drugs due to their electrophilic reactivity. Zomepirac (ZP) was withdrawn from the market because of adverse effects such as renal toxicity. Although ZP is mainly metabolized to acyl glucuronide (ZP-AG) by UDP-glucuronosyltransferase, the role of ZP-AG in renal toxicity is unknown. In this study, we established a ZP-induced kidney injury mouse model by pretreatment with tri-o-tolyl phosphate (TOTP), a nonselective esterase inhibitor, and l-buthionine-(S,R)-sulfoximine (BSO), a glutathione synthesis inhibitor. The role of ZP-AG in renal toxicity was investigated using this model. The model showed significant increases in blood urea nitrogen (BUN) and creatinine (CRE), but not alanine aminotransferase. The ZP-AG concentrations were elevated by cotreatment with TOTP in the plasma and liver and especially in the kidney. The ZP-AG concentrations in the kidney correlated with values for BUN and CRE. Upon histopathological examination, vacuoles and infiltration of mononuclear cells were observed in the model mouse. In addition to immune-related responses, oxidative stress markers, such as the glutathione/disulfide glutathione ratio and malondialdehyde levels, were different in the mouse model. The suppression of ZP-induced kidney injury by tempol, an antioxidant agent, suggested the involvement of oxidative stress in ZP-induced kidney injury. This is the first study to demonstrate that AG accumulation in the kidney by TOTP and BSO treatment could explain renal toxicity and to show the in vivo toxicological potential of AGs.
Asunto(s)
Lesión Renal Aguda/inducido químicamente , Riñón/efectos de los fármacos , Tolmetina/análogos & derivados , Lesión Renal Aguda/sangre , Lesión Renal Aguda/patología , Lesión Renal Aguda/prevención & control , Animales , Antioxidantes/farmacología , Biomarcadores/sangre , Biotransformación , Nitrógeno de la Urea Sanguínea , Butionina Sulfoximina/farmacología , Creatinina/sangre , Óxidos N-Cíclicos/farmacología , Relación Dosis-Respuesta a Droga , Inhibidores Enzimáticos/farmacología , Femenino , Mediadores de Inflamación/metabolismo , Riñón/metabolismo , Riñón/patología , Ratones Endogámicos BALB C , Estrés Oxidativo/efectos de los fármacos , Marcadores de Spin , Factores de Tiempo , Tolmetina/administración & dosificación , Tolmetina/sangre , Tolmetina/toxicidad , Tritolilfosfatos/farmacologíaRESUMEN
OBJECTIVE: While previous research has demonstrated roller compaction operating parameters strongly influence the properties of the final product, a greater emphasis might be placed on the raw material attributes of the formulation. There were two main objectives to this study. First, to assess the effects of different process variables on the properties of the obtained ribbons and downstream granules produced from the rolled compacted ribbons. Second, was to establish if models obtained with formulations of one active pharmaceutical ingredient (API) could predict the properties of similar formulations in terms of the excipients used, but with a different API. MATERIALS AND METHODS: Tolmetin and acetaminophen, chosen for their different compaction properties, were roller compacted on Fitzpatrick roller compactor using the same formulation. Models created using tolmetin and tested using acetaminophen. The physical properties of the blends, ribbon, granule and tablet were characterized. Multivariate analysis using partial least squares was used to analyze all data. RESULTS: Multivariate models showed that the operating parameters and raw material attributes were essential in the prediction of ribbon porosity and post-milled particle size. The post compacted ribbon and granule attributes also significantly contributed to the prediction of the tablet tensile strength. CONCLUSIONS: Models derived using tolmetin could reasonably predict the ribbon porosity of a second API. After further processing, the post-milled ribbon and granules properties, rather than the physical attributes of the formulation were needed to predict downstream tablet properties. An understanding of the percolation threshold of the formulation significantly improved the predictive ability of the models.
Asunto(s)
Acetaminofén/administración & dosificación , Excipientes/química , Modelos Químicos , Tolmetina/administración & dosificación , Acetaminofén/química , Química Farmacéutica/métodos , Composición de Medicamentos/métodos , Análisis de los Mínimos Cuadrados , Análisis Multivariante , Tamaño de la Partícula , Porosidad , Comprimidos , Resistencia a la Tracción , Tolmetina/químicaRESUMEN
AIM: In order to avoid gastric irritation caused by tolmetin sodium (TS), gastro resistant Eudragit® S 100 microsphere formulations were prepared with the emulsion/solvent diffusion method. MATERIALS: Considering the high water solubility of the TS molecule, the effects of the presence of inorganic salt (NaCl, NaBr and KH2PO4; 0.1 M and 1.0 M) in external phase and external phase pH on the encapsulation efficiency were evaluated. RESULTS: Percentage yield value was found to vary between 55.8% and 72.1%. Improvement in encapsulation efficiency was determined by increasing concentrations of NaCl, NaBr and KH2PO4. The microspheres were observed to have a spherical shape and the measured particle size values varied between 52.1 and 81.5 µm. The released amounts of the drug were found to be low as the inorganic salt concentrations increased. CONCLUSION: Conclusively, drug release in stomach pH was significantly prevented by the microspheres prepared using Eudragit® S 100 polymer, and these formulations are considered to be a model for other orally administered drugs with similar problems.
Asunto(s)
Antiinflamatorios no Esteroideos/administración & dosificación , Microesferas , Ácidos Polimetacrílicos/química , Tolmetina/administración & dosificación , Antiinflamatorios no Esteroideos/efectos adversos , Antiinflamatorios no Esteroideos/química , Química Farmacéutica , Difusión , Emulsiones , Concentración de Iones de Hidrógeno , Interacciones Hidrofóbicas e Hidrofílicas , Tamaño de la Partícula , Sales (Química)/química , Solubilidad , Solventes/química , Tolmetina/efectos adversos , Tolmetina/químicaRESUMEN
BACKGROUND: Mefenamic acid is a non-steroidal anti-inflammatory drug (NSAID). It is most often used for treating pain of dysmenorrhoea in the short term (seven days or less), as well as mild to moderate pain including headache, dental pain, postoperative and postpartum pain. It is widely available in many countries worldwide. OBJECTIVES: To assess the efficacy of single dose oral mefenamic acid in acute postoperative pain, and any associated adverse events. SEARCH STRATEGY: We searched Cochrane CENTRAL, MEDLINE, EMBASE and the Oxford Pain Relief Database for studies to December 2010. SELECTION CRITERIA: Single oral dose, randomised, double-blind, placebo-controlled trials of mefenamic acid for relief of established moderate to severe postoperative pain in adults. DATA COLLECTION AND ANALYSIS: Studies were assessed for methodological quality and the data extracted by two review authors independently. Summed total pain relief (TOTPAR) or pain intensity difference (SPID) over 4 to 6 hours was used to calculate the number of participants achieving at least 50% pain relief. These derived results were used to calculate, with 95% confidence intervals, the relative benefit compared to placebo, and the number needed to treat (NNT) for one participant to experience at least 50% pain relief over 4 to 6 hours. 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 was collected. MAIN RESULTS: Four studies with 842 participants met the inclusion criteria; 126 participants were treated with mefenamic acid 500 mg, 67 with mefenamic acid 250 mg, 197 with placebo, and 452 with lignocaine, aspirin, zomepirac or nimesulide. Participants had pain following third molar extraction, episiotomy and orthopaedic surgery. The NNT for at least 50% pain relief over 6 hours with a single dose of mefenamic acid 500 mg compared to placebo was 4.0 (2.7 to 7.1), and the NNT to prevent use of rescue medication over 6 hours was 6.5 (3.6 to 29). There were insufficient data to analyse other doses or active comparators, or numbers of participants experiencing any adverse events. No serious adverse events or adverse event withdrawals were reported in these studies. AUTHORS' CONCLUSIONS: Oral mefenamic acid 500 mg was effective at treating moderate to severe acute postoperative pain, based on limited data. Efficacy of other doses, and safety and tolerability could not be assessed.
Asunto(s)
Antiinflamatorios no Esteroideos/administración & dosificación , Ácido Mefenámico/administración & dosificación , Dolor Postoperatorio/tratamiento farmacológico , Enfermedad Aguda , Administración Oral , Adulto , Antiinflamatorios no Esteroideos/uso terapéutico , Aspirina/administración & dosificación , Aspirina/uso terapéutico , Humanos , Ácido Mefenámico/uso terapéutico , Ensayos Clínicos Controlados Aleatorios como Asunto , Sulfonamidas/administración & dosificación , Sulfonamidas/uso terapéutico , Tolmetina/administración & dosificación , Tolmetina/análogos & derivados , Tolmetina/uso terapéuticoRESUMEN
BACKGROUND: Fenoprofen is a non-steroidal anti-inflammatory drug (NSAID), available in several different countries, but not widely used. OBJECTIVES: To assess the efficacy of single dose oral fenoprofen in acute postoperative pain, and associated adverse events. SEARCH STRATEGY: We searched Cochrane CENTRAL, MEDLINE, EMBASE and the Oxford Pain Relief Database for studies to December 2010. SELECTION CRITERIA: Single oral dose, randomised, double-blind, placebo-controlled trials of fenoprofen for relief of established moderate to severe postoperative pain in adults. DATA COLLECTION AND ANALYSIS: Studies were assessed for methodological quality and data extracted by two review authors independently. Summed total pain relief (TOTPAR) or pain intensity difference (SPID) over 4 to 6 hours was used to calculate the number of participants achieving at least 50% pain relief. These derived results were used to calculate, with 95% confidence intervals, the relative benefit compared to placebo, and the number needed to treat (NNT) for one participant to experience at least 50% pain relief over 4 to 6 hours. 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 was collected. MAIN RESULTS: Five studies (696 participants) met the inclusion criteria; 24 participants were treated with fenoprofen 12.5 mg, 23 with fenoprofen 25 mg, 79 with fenoprofen 50 mg, 78 with fenoprofen 100 mg, 146 with fenoprofen 200 mg, 55 with fenoprofen 300 mg, 43 with zomepirac 100 mg, 30 with morphine 8 mg, 77 with codeine 60 mg, and 141 with placebo. Participants had pain following third molar extraction, laparoscopy, minor day surgery and episiotomy. The NNT for at least 50% pain relief over 4 to 6 hours with a single dose of fenoprofen 200 mg compared to placebo was 2.3 (1.9 to 3.0). There were insufficient data to analyse other doses or active comparators, time to use of rescue medication, or numbers of participants needing rescue medication. There was no difference in numbers of participants experiencing any adverse events between fenoprofen 200 mg and placebo. No serious adverse events or adverse event withdrawals were reported in these studies. AUTHORS' CONCLUSIONS: Oral fenoprofen 200 mg is effective at treating moderate to severe acute postoperative pain, based on limited data for at least 50% pain relief over 4 to 6 hours. Efficacy of other doses, other efficacy outcomes, and safety and tolerability could not be assessed.
Asunto(s)
Antiinflamatorios no Esteroideos/administración & dosificación , Fenoprofeno/administración & dosificación , Dolor Postoperatorio/tratamiento farmacológico , Enfermedad Aguda , Administración Oral , Adulto , Analgésicos Opioides/administración & dosificación , Codeína/administración & dosificación , Humanos , Morfina/administración & dosificación , Tolmetina/administración & dosificación , Tolmetina/análogos & derivadosRESUMEN
BACKGROUND: Ibuprofen and tolmetin are popular non-steroidal anti-inflammatory drugs. Previous animal studies taken with single daily doses showed their good prenatal tolerability. However, since both cyclooxygenase (COX) inhibitors have a short half-life, the current report presents drug developmental effects after triple daily doses administration, as they are used in human. METHODS: Drugs were separately, orally dosed to pregnant rats triple daily 8 hr apart from day 8 to 21 (GD=1-plug day). The total daily doses were set at 25.5, 255.0, and 600.0 mg/kg for ibuprofen and 25.5, 255.0, and 2550.0 mg/kg for tolmetin. Fetuses were delivered on GD 21 and routinely examined. Comprehensive clinical and developmental measurements were done. RESULTS: Maternal toxicity and intrauterine growth retardation were found in groups exposed to the highest doses of both drugs. An increase of external variations was reported in groups exposed to the middle and highest dose of ibuprofen and to the highest dose of tolmetin. Skeletal variations were significantly different only in litters treated with the highest doses of the drugs. Pooled statistical analysis showed a higher incidence of midline and ventricular septal (VSD) defect in rat fetuses exposed to COX inhibitors when compared with historical control data. For ibuprofen, the influence on VSD was similar to aspirin. CONCLUSION: Both COX inhibitors were toxic to dams in the highest doses evaluated, which caused a significantly greater incidence of intrauterine growth retardation and developmental variations.
Asunto(s)
Inhibidores de la Ciclooxigenasa/toxicidad , Desarrollo Fetal/efectos de los fármacos , Ibuprofeno/toxicidad , Tolmetina/toxicidad , Animales , Aspirina/toxicidad , Peso Corporal/efectos de los fármacos , Inhibidores de la Ciclooxigenasa/administración & dosificación , Inhibidores de la Ciclooxigenasa/farmacología , Relación Dosis-Respuesta a Droga , Femenino , Retardo del Crecimiento Fetal/inducido químicamente , Feto/anomalías , Feto/efectos de los fármacos , Defectos del Tabique Interventricular/inducido químicamente , Ibuprofeno/administración & dosificación , Exposición Materna , Embarazo , Ratas , Ratas Wistar , Tolmetina/administración & dosificaciónRESUMEN
Non-steroidal anti-inflammatory drugs (NSAIDs) are prohibited by the International Federation of Horse Racing Authorities but are commonly used in veterinary practice. Plasma and urinary concentrations of the NSAID tolmetin were determined by a high-performance liquid chromatographic procedure with UV detection following oral administration of a dose of 1 g to six fasted untrained standard bred mares. With a limit of quantitation (LOQ) of 0.05 microg/ml tolmetin was present in plasma for 9-12 h post-administration. Maximum concentrations of 2.1+/-0.89 microg/ml were found after 0.7+/-0.25 h. The elimination half-life was 2+/-1.25 h. Plasma protein binding at concentrations of 0.25 and 2.5 microg/ml was 92+/-4.9 and 84+/-4.2%, respectively. As early as 1 h after dosage, tolmetin could be detected in unhydrolysed urine and remained detectable up to 48 h (LOQ=0.5 microg/ml). The maximum concentrations occurred 1.8+/-0.4 h after administration. The percentage of the dose excreted as unchanged tolmetin within 12 h was 58+/-7.9%. Neither conjugates nor metabolites could be detected under the experimental conditions studied. For confirmatory analysis in doping control, an LC-MS method was developed. Analysis was performed on an ion trap LC-MS system equipped with an ESI probe in positive MS(2) mode.
Asunto(s)
Caballos/sangre , Tolmetina/sangre , Administración Oral , Animales , Cromatografía Líquida de Alta Presión/métodos , Femenino , Tolmetina/administración & dosificación , Tolmetina/químicaRESUMEN
In a previous paper the preparation has been described, by three different techniques, of microparticles made of Eudragit RS 100 and RL 100 containing a NSAI agent, Tolmetin. Freely flowing microparticles failed to affect significantly the in vitro drug release, which displayed a similar dissolution profile after micro-encapsulation to the free drug powder. Microparticles were then converted into tablets and the effect of compression on drug delivery, as well as that of the presence of co-additives, was studied in the present work. Furthermore, microparticles were also prepared by adding MgO to the polymer matrix, to reduce the sensitivity of the drug to pH changes during its dissolution. Similarly, magnesium stearate was also used for microparticle formation as a droplet stabilizer, in order to reduce particle size and hinder rapid drug release. A mathematical evaluation, by using two semi-empirical equations, was applied to evaluate the influence of dissolution and diffusion phenomena upon drug release from microparticle tablets.
Asunto(s)
Antiinflamatorios no Esteroideos/química , Tolmetina/química , Resinas Acrílicas , Algoritmos , Antiinflamatorios no Esteroideos/administración & dosificación , Composición de Medicamentos , Excipientes , Concentración de Iones de Hidrógeno , Cinética , Óxido de Magnesio/química , Microesferas , Solubilidad , Solventes , Ácidos Esteáricos/química , Comprimidos , Tolmetina/administración & dosificaciónAsunto(s)
Ensayos Clínicos Controlados Aleatorios como Asunto/métodos , Acetaminofén/administración & dosificación , Acetaminofén/análogos & derivados , Acetaminofén/uso terapéutico , Antiinflamatorios no Esteroideos/administración & dosificación , Antiinflamatorios no Esteroideos/uso terapéutico , Relación Dosis-Respuesta a Droga , Humanos , Ketorolaco , Dolor Postoperatorio/tratamiento farmacológico , Placebos , Proyectos de Investigación , Tolmetina/administración & dosificación , Tolmetina/análogos & derivados , Tolmetina/uso terapéuticoRESUMEN
PURPOSE: To compare the 2 most popular commercially available topical nonsteroidal anti-inflammatory drugs (NSAIDs) in the treatment of ocular pain following radial keratotomy (RK). SETTING: Multicenter clinical trial. METHODS: Ninety-seven RK patients were randomly assigned to 1 of 3 treatment groups: ketorolac tromethamine, diclofenac sodium, and moist drops as a control. The patients used 1 drop of the masked medication and 1 drop of ofloxacin 3 times a day for 3 days prior to surgery. They received 1 drop of the masked medication 1 hour before surgery, immediately after surgery, and 4 times a day thereafter. Patients were given a written questionnaire preoperatively and were also instructed to call a central computerized telephone system to answer prerecorded questions about ocular comfort. The calls were placed 30 minutes and 1, 2, 3, 4, 5, 6, 24, and 48 hours after surgery. RESULTS: Two hundred ten statistical values were calculated to compare symptoms in the unoperated eye at baseline with symptoms in the operated eyes at each of 9 postoperative time points. Only 7 of the 210 values (3.3%) were significantly different among patient groups (operated versus unoperated eyes) by psychometric testing. CONCLUSIONS: Both ketorolac tromethamine and diclofenac sodium were more effective in reducing post-RK discomfort than the control (moist artificial tears). Given the large number of tests and the small number that tested as significant, the significant differences (7 of 210 measurements) observed among the 3 treatment groups probably occurred by chance, although the improved foreign-body sensation, functionality, and compliance scores in the ketorolac group during the first 4 hours might be clinically important.
Asunto(s)
Antiinflamatorios no Esteroideos/uso terapéutico , Diclofenaco/uso terapéutico , Queratotomía Radial/efectos adversos , Dolor Postoperatorio/tratamiento farmacológico , Tolmetina/análogos & derivados , Trometamina/análogos & derivados , Adulto , Antiinflamatorios no Esteroideos/administración & dosificación , Diclofenaco/administración & dosificación , Método Doble Ciego , Femenino , Humanos , Ketorolaco Trometamina , Masculino , Persona de Mediana Edad , Miopía/cirugía , Soluciones Oftálmicas/administración & dosificación , Soluciones Oftálmicas/uso terapéutico , Dolor Postoperatorio/etiología , Estudios Prospectivos , Encuestas y Cuestionarios , Tolmetina/administración & dosificación , Tolmetina/uso terapéutico , Trometamina/administración & dosificación , Trometamina/uso terapéutico , Agudeza VisualRESUMEN
We conducted a prospective, randomised, double-blind study to compare the analgesic efficacy of intravenous tramadol 1.5 mg.kg-1 and ketorolac 10 mg in 60 ASA grade 1 and 2 patients scheduled to undergo day-case laparoscopic sterilisation by application of Filshie clips. Patients who received tramadol had significantly less postoperative pain in the recovery room (p = 0.007) and at discharge from the day-surgery unit (p = 0.03), and they required rescue analgesia with morphine less often (p = 0.02) than patients who received ketorolac. No difference in either the incidence or severity of nausea and vomiting was observed between the two groups. Both analgesic drugs were well tolerated at the doses given in the study, although dry mouth was significantly more common after the administration of tramadol (p = 0.009). Three patients in the tramadol group and five in the ketorolac group required overnight admission due to pain or nausea and vomiting.
Asunto(s)
Procedimientos Quirúrgicos Ambulatorios , Analgesia , Analgésicos no Narcóticos/administración & dosificación , Analgésicos Opioides/administración & dosificación , Esterilización Tubaria , Tolmetina/análogos & derivados , Tramadol/administración & dosificación , Adulto , Método Doble Ciego , Femenino , Humanos , Inyecciones Intravenosas , Ketorolaco , Laparoscopía , Dimensión del Dolor , Dolor Postoperatorio/prevención & control , Estudios Prospectivos , Tolmetina/administración & dosificaciónRESUMEN
Spondylolisthesis, the anterior or posterior displacement of one vertebra on another, usually affects the lumbar region. Five percent of the population has one of the five classes of spondylolisthesis, which include dysplastic, isthmic, degenerative, traumatic, and pathologic spondylolisthesis. This article focuses on the dysplastic type, which makes up 14% to 21% of all spondylolisthesis. Dysplastic spondylolisthesis usually causes no symptoms in children; pain usually begins in adolescence. The key to diagnosis is the appropriate use of radiography in the evaluation of low back pain. This report describes a case involving a 21-year-old woman presenting with back pain to the family physician. Also, it details how the diagnosis was achieved and evaluates conservative and aggressive treatment options.
Asunto(s)
Vértebras Lumbares/patología , Espondilolistesis/diagnóstico , Espondilolistesis/terapia , Adulto , Analgésicos no Narcóticos/administración & dosificación , Antiinflamatorios no Esteroideos/administración & dosificación , Terapia Combinada , Femenino , Humanos , Inyecciones Intramusculares , Ketorolaco , Imagen por Resonancia Magnética , Ortopedia/métodos , Pronóstico , Tolmetina/administración & dosificación , Tolmetina/análogos & derivadosAsunto(s)
Analgésicos no Narcóticos/administración & dosificación , Antipsicóticos/administración & dosificación , Trastornos Migrañosos/tratamiento farmacológico , Proclorperazina/administración & dosificación , Tolmetina/análogos & derivados , Femenino , Humanos , Infusiones Intravenosas , Ketorolaco , Masculino , Ensayos Clínicos Controlados Aleatorios como Asunto , Tolmetina/administración & dosificaciónRESUMEN
OBJECTIVE: To compare the efficacy and safety of two analgesics (tramadol and ketorolac) for initial emergency treatment of renal colic. METHODS: A prospective study on 48 patients randomly assigned to treatment with ketorolac 30 mg i.m. and tramadol 1 mg/kg s.c. Pain intensity was evaluated by a simple analogic scale ranging from 0-4 (0 = no pain, 1 = mild, 2 = moderate, 3 = severe and 4 = very severe pain). Statistical analyses were performed with Student's test and the chi square test for numerical and qualitative data, respectively. RESULTS: No significant differences were found for the overall efficacy (> 80%) or side effects in both groups. However, a difference was found between both groups for pain score 15 minutes post-injection, which showed i.m. ketorolac to be more effective. CONCLUSION: Both ketorolac (30 mg i.m.) and tramadol (1 mg/kg s.c.) are effective in the initial treatment of renal colic. Both drugs have an efficacy greater than 80% when used separately and almost 100% when used in combination. The analgesic effect of ketorolac is observed earlier than that of tramadol.
Asunto(s)
Analgésicos no Narcóticos/administración & dosificación , Analgésicos Opioides/administración & dosificación , Cólico/tratamiento farmacológico , Enfermedades Renales/tratamiento farmacológico , Tolmetina/análogos & derivados , Tramadol/administración & dosificación , Urgencias Médicas , Humanos , Inyecciones Intramusculares , Inyecciones Subcutáneas , Ketorolaco , Dimensión del Dolor , Estudios Prospectivos , Tolmetina/administración & dosificaciónRESUMEN
Oxadol (nefopam hydrochloride), a central analgesic, was used for postoperative pain relief in patients operated on the abdominal and pelvic organs for cancer. The analgesic effect of oxadol was sufficient for arresting moderate postoperative pain. Although the drug exerts rather many side effects, none of them notably deteriorated the clinical status of patients.
Asunto(s)
Analgésicos no Narcóticos/uso terapéutico , Nefopam/uso terapéutico , Dolor Postoperatorio/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Analgésicos no Narcóticos/administración & dosificación , Analgésicos Opioides/administración & dosificación , Analgésicos Opioides/uso terapéutico , Butorfanol/administración & dosificación , Butorfanol/uso terapéutico , Femenino , Neoplasias Gastrointestinales/cirugía , Neoplasias de los Genitales Femeninos/cirugía , Humanos , Hidrocortisona/sangre , Ketorolaco Trometamina , Masculino , Persona de Mediana Edad , Nefopam/administración & dosificación , Dolor Postoperatorio/sangre , Tolmetina/administración & dosificación , Tolmetina/análogos & derivados , Tolmetina/uso terapéutico , Trometamina/administración & dosificación , Trometamina/análogos & derivados , Trometamina/uso terapéuticoRESUMEN
This multicenter, double-masked, randomized, parallel study compared the efficacy and safety profile of ketorolac tromethamine 0.5% ophthalmic solution with that of its vehicle in the maintenance of pupillary mydriasis during cataract surgery. A total of 176 adult patients scheduled to undergo unilateral extracapsular cataract extraction and posterior-chamber intraocular lens implantation received either ketorolac tromethamine 0.5% (n = 89) or vehicle (n = 87), starting 2 hours before surgery. One drop of study medication was instilled every 30 minutes for a total of 4 drops. No epinephrine was used in the intraoperative irrigating solution. Pupil diameter was measured with a caliper at 3 time points during surgery. To ensure participant safety, biomicroscopy, ophthalmoscopy, intraocular pressure, adverse events, and preoperative and postoperative visual acuity and refractive error were also monitored. The mean change in horizontal and vertical pupil diameter from the time of the first incision to after cortical irrigation and aspiration was significantly less with active ketorolac than with vehicle (P < or = 0.014). Consequently, mean pupil diameter after cortical irrigation and aspiration was significantly greater with ketorolac than with vehicle (P < or = 0.030). No significant between-group differences were observed in the change in pupil diameter between the end of surgery and postoperative administration of a miotic agent, safety variables, or occurrence of adverse events. In this study, ketorolac tromethamine 0.5% ophthalmic solution provided effective and well-tolerated inhibition of surgically induced miosis during cataract surgery.
Asunto(s)
Antiinflamatorios no Esteroideos/uso terapéutico , Extracción de Catarata , Miosis/prevención & control , Complicaciones Posoperatorias/prevención & control , Tolmetina/análogos & derivados , Trometamina/análogos & derivados , Anciano , Anciano de 80 o más Años , Antiinflamatorios no Esteroideos/administración & dosificación , Método Doble Ciego , Femenino , Humanos , Ketorolaco Trometamina , Masculino , Persona de Mediana Edad , Soluciones Oftálmicas , Tolmetina/administración & dosificación , Tolmetina/uso terapéutico , Trometamina/administración & dosificación , Trometamina/uso terapéuticoRESUMEN
BACKGROUND AND OBJECTIVES: Morphine and nonsteroidal antiinflammatory drugs (NSAID) have been found to be effective in relieving postoperative pain. The goal of this study was to determine whether ketorolac alone or in combination with morphine provides superior pain relief following arthroscopy performed with local anesthesia (LA). METHODS: This was a randomized, double-blind, prospective, study in 100 healthy patients from 15 to 60 years of age. Knee arthroscopy was performed with LA using 40 mL prilocaine (5 mg/mL) with adrenaline (4 microg/mL). At the end of the operation, a catheter was inserted intra-articularly, and one of the following solutions diluted to a total volume of 40 mL was injected: group P (40 mL normal saline), group M (3 mg morphine), group K30 (30 mg ketorolac), group K60 (60 mg ketorolac), and group KM (3 mg morphine + 30 mg ketorolac). Visual analog scale (VAS) pain scores (0-100 mm) were measured preoperative and at 30, 60, 90, 120 minutes postoperative and thereafter 4, 8, 24, and 48 hours at rest and on movement of the knee. The total number of distalgesic tablets (325 mg paracetamol + 32.5 mg dextropropoxyphene) consumed during the 48 hours postoperative was recorded. RESULTS: Significant differences in VAS pain scores were seen between group P and group KM at 4, 8, and 24 hours (P < .05) and between group M and group KM at 4, 8, 24, and 48 hours (P < .01) after the operation at rest. During mobilization of the knee, a significant difference in VAS pain score was found between group P and group KM at 8, 24, and 48 hours (P < .05) and between group P and group K60 at 24 and 48 hours (P < .05). The total consumption of distalgesic tablets did not differ among the groups. CONCLUSIONS: The combination of 3 mg morphine plus 30 mg ketorolac provided significantly better analgesia than either placebo alone or morphine alone. This result could be a synergistic effect.
Asunto(s)
Analgésicos no Narcóticos/administración & dosificación , Analgésicos Opioides/administración & dosificación , Anestesia Local/métodos , Articulación de la Rodilla/cirugía , Morfina/administración & dosificación , Dolor Postoperatorio/tratamiento farmacológico , Tolmetina/análogos & derivados , Adolescente , Adulto , Artroscopía/efectos adversos , Método Doble Ciego , Quimioterapia Combinada , Femenino , Humanos , Inyecciones Intraarticulares , Ketorolaco , Masculino , Persona de Mediana Edad , Dimensión del Dolor/efectos de los fármacos , Estudios Prospectivos , Tolmetina/administración & dosificaciónRESUMEN
PURPOSE: To compare the anti-inflammatory and analgesic efficacy and safety of ketorolac tromethamine 0.5% ophthalmic solution with those of prednisolone acetate 1% in patients having cataract surgery. SETTING: Shawnee Mission Eye Care, Shawnee Mission, Kansas, USA. METHODS: This double-blind, randomized, single-site study comprised 59 healthy men and women with a clinical diagnosis of routine ocular cataract requiring surgical removal. All patients had extracapsular cataract extraction and posterior chamber intraocular lens implantation. After surgery, patients were randomized to receive ketorolac tromethamine 0.5% or prednisolone acetate 1%, self-instilled in the treated eye, according to the following schedule: 1 to 2 drops 4 times daily (week 1); 3 times daily (week 2); 2 times daily (week 3); once daily (week 4). Patients were examined postoperatively on days 1, 7, and 28. Intraocular anti-inflammatory efficacy was assessed by lid edema, lid injection, conjunctival injection, corneal edema, ciliary flush, and anterior chamber cells. Analgesic efficacy was assessed by patient self-rated pain severity, pain frequency, total symptom sum, and overall global improvement. RESULTS: Both treatments produced comparable reductions in intraocular inflammation and pain after cataract surgery and were well tolerated by patients. No adverse events were reported, and there were no significant changes in intraocular pressure in either group. Improvements in visual acuity were also similar in both groups. CONCLUSION: Ketorolac tromethamine 0.5% ophthalmic solution was as effective and well-tolerated as prednisolone acetate 1% solution in controlling postoperative inflammation and pain after cataract surgery.
Asunto(s)
Antiinflamatorios no Esteroideos/uso terapéutico , Antiinflamatorios/uso terapéutico , Extracción de Catarata , Complicaciones Posoperatorias/prevención & control , Prednisolona/análogos & derivados , Tolmetina/análogos & derivados , Trometamina/análogos & derivados , Adulto , Anciano , Anciano de 80 o más Años , Antiinflamatorios/administración & dosificación , Antiinflamatorios no Esteroideos/administración & dosificación , Método Doble Ciego , Femenino , Estudios de Seguimiento , Humanos , Ketorolaco Trometamina , Implantación de Lentes Intraoculares , Masculino , Persona de Mediana Edad , Soluciones Oftálmicas/administración & dosificación , Soluciones Oftálmicas/uso terapéutico , Dimensión del Dolor , Prednisolona/administración & dosificación , Prednisolona/uso terapéutico , Estudios Retrospectivos , Seguridad , Tolmetina/administración & dosificación , Tolmetina/uso terapéutico , Resultado del Tratamiento , Trometamina/administración & dosificación , Trometamina/uso terapéutico , Uveítis Anterior/prevención & control , Agudeza VisualRESUMEN
OBJECTIVE: To compare the pharmacokinetics and metabolism of R(+)- and S(-)- ketorolac in children. METHODS: Children from 3 to 18 years old received 0.6 mg/kg racemic ketorolac intravenously. Serial blood samples were obtained for 12 hours, and urine was collected for 12 to 24 hours. Racemic ketorolac was measured in plasma, and racemic ketorolac, para-hydroxyketorolac, and ketorolac glucuronide were measured in urine by HPLC. S(-)- and R(+)-ketorolac were measured in plasma; S(-)- and R(+)-ketorolac and ketorolac glucuronide were measured in urine by chiral HPLC separation. Plasma pharmacokinetic parameters for racemic drug and both enantiomers were determined for each patient. RESULTS: Clearance of racemic ketorolac in children was approximately 2 times the clearance reported in adults. Clearance of the S(-) enantiomer was 4 times that of the R(+) enantiomer. Terminal half-life of S(-)-ketorolac was 40% that of the R(+) enantiomer, and the apparent volume of distribution of the S(-) enantiomer was greater than that of the R(+) form. Recovery of S(-)-ketorolac glucuronide was 2.3 times that of the R(+) enantiomer. CONCLUSION: The higher clearance in children suggests that the weight-adjusted dose of ketorolac may have to be greater for children to achieve plasma concentrations comparable to those of adults. Because of the greater clearance and shorter half-life of S(-)-ketorolac, pharmacokinetic predictions based on racemic assays may overestimate the duration of pharmacologic effect. Enantiomeric pharmacokinetic differences are best explained by stereoselective plasma protein binding. Selective glucuronidation of the S(-) enantiomer suggests that stereoselective metabolism may also be a contributing factor.