RESUMEN
BACKGROUND: Musculoskeletal disorders are an important cause of work absence. Clinical practice guidelines recommend nonsteroidal anti-inflammatory drugs (NSAIDs) for grade I-II cervical sprains. The combination of thiamine + pyridoxine + cyanocobalamin vitamins has been used, alone and in combination with NSAIDs, for pain and inflammation in musculoskeletal disorders. OBJECTIVE: The objective of this study was to demonstrate the analgesic synergy of dexketoprofen, and the combination of vitamins thiamine + pyridoxine + cyanocobalamin in a fixed-dose combination (FDC) for the treatment of acute pain caused by grade I-II cervical sprains. METHODS: We conducted a multicentre, prospective, randomized, double-blind, phase IIIb clinical study comparing two treatment groups: (1) dexketoprofen 25 mg/vitamin B (thiamine 100 mg, pyridoxine 50 mg and cyanocobalamin 0.50 mg) in an FDC (two or more active ingredients combined in a single dosage form) versus (2) dexketoprofen 25 mg monotherapy (single drug to treat a particular disease), one capsule or tablet orally, every 8 h for 7 days. Final mean, average change, and percentage change in pain perception (measured using a visual analogue scale [VAS]) were compared with baseline between groups. A p value < 0.05 was considered statistically significant. Analyses were conducted using SPSS software, v.29.0. RESULTS: A statistically significant reduction in pain intensity was observed from the third day of treatment with the FDC compared with monotherapy (- 3.1 ± - 1.5 and - 2.6 ± - 1.1 cm, respectively) measured using the VAS (p = 0.011). Regarding the degree of disability, using the Northwick Park Neck Pain Questionnaire (NPQ), statistical difference was observed for the final measurement (7.5%, interquartile range [IQR] 2.5, 10.5; vs. 7.9%, IQR 5.0, 13.8; p = 0.028). A lower proportion of adverse events was reported when using the FDC. CONCLUSIONS: The FDC of dexketoprofen/thiamine + pyridoxine + cyanocobalamin vitamins demonstrated superior efficacy and a better safety profile compared with dexketoprofen monotherapy for pain treatment in patients with grade I-II cervical sprains. CLINICAL TRIALS REGISTRATION: NCT05001555, registered 29 July 2021 ( https://clinicaltrials.gov/study/NCT05001555 ).
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Antiinflamatorios no Esteroideos , Combinación de Medicamentos , Cetoprofeno , Piridoxina , Tiamina , Trometamina , Vitamina B 12 , Humanos , Método Doble Ciego , Tiamina/administración & dosificación , Tiamina/análogos & derivados , Tiamina/uso terapéutico , Cetoprofeno/administración & dosificación , Cetoprofeno/análogos & derivados , Femenino , Adulto , Piridoxina/administración & dosificación , Piridoxina/uso terapéutico , Masculino , Antiinflamatorios no Esteroideos/administración & dosificación , Vitamina B 12/análogos & derivados , Vitamina B 12/administración & dosificación , Vitamina B 12/uso terapéutico , Persona de Mediana Edad , Trometamina/administración & dosificación , Estudios Prospectivos , Complejo Vitamínico B/administración & dosificación , Complejo Vitamínico B/uso terapéutico , Dimensión del Dolor/métodos , Adulto JovenRESUMEN
Rifampicin (RIF) is an antibiotic used to treat tuberculosis and leprosy. Even though RIF is a market-available drug, it has a low aqueous solubility, hindering its bioavailability. Among the strategies for bioavailability improvement of poorly soluble drugs, coamorphous systems have been revealed as an alternative in the increase of the aqueous solubility of drug systems and at the same time also increasing the amorphous state stability and dissolution rate when compared with the neat drug. In this work, a new coamorphous form from RIF and tromethamine (TRIS) was synthesized by slow evaporation. Structural, electronic, and thermodynamic properties and solvation effects, as well as drug-coformer intermolecular interactions, were studied through density functional theory (DFT) calculations. Powder X-ray diffraction (PXRD) data allowed us to verify the formation of a new coamorphous. In addition, the DFT study indicates a possible intermolecular interaction by hydrogen bonds between the available amino and carbonyl groups of RIF and the hydroxyl and amino groups of TRIS. The theoretical spectra obtained are in good agreement with the experimental data, suggesting the main interactions occurring in the formation of the coamorphous system. PXRD was used to study the physical stability of the coamorphous system under accelerated ICH conditions (40 °C and 75% RH), indicating that the material remained in an amorphous state up to 180 days. The thermogravimetry result of this material showed a good thermal stability up to 153 °C, and differential scanning calorimetry showed that the glass temperature (Tg) was at 70.0 °C. Solubility studies demonstrated an increase in the solubility of RIF by 5.5-fold when compared with its crystalline counterpart. Therefore, this new material presents critical parameters that can be considered in the development of new coamorphous formulations.
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Rifampin , Trometamina , Composición de Medicamentos , Solubilidad , Agua , Modelos Teóricos , Estabilidad de Medicamentos , Rastreo Diferencial de Calorimetría , Difracción de Rayos XRESUMEN
O uso de diluentes adequados é importante para o sucesso da inseminação artificial. O objetivo deste estudo foi avaliar a eficiência de diluentes em diferentes temperaturas. Foram utilizados os seguintes diluentes: Beltsville Thwaing Solution (BTS); TRIS (Tris-hidroximetil-aminometano - H2NC(CH2OH)3); TRIS + gema de ovo (TGO) e Leite em pó desnatado (LPD). Cinquenta ejaculados foram analisados quanto ao vigor, à motilidade, à funcionalidade de membrana e à atividade mitocondrial. Os diluentes TGO e LPD mantiveram os maiores valores para vigor e motilidade a 10 °C, em comparação aos demais tratamentos (p<0,05). A 17 °C, esses diluentes apresentaram resultados melhores de vigor e motilidade em relação aos demais, somente até D1 (p<0,05). A partir de D2, o BTS mostrou-se como o melhor diluente para a preservação dessas características. Maior percentual de espermatozoides com membrana funcional foi observado no TGO a 10 °C, seguido do LPD, BTS e TRIS (p<0,05). A 17 °C, o BTS manteve essa característica, exceto em D0, em que o TGO e o LPD apresentaram melhores resultados. Quanto a atividade mitocondrial, maiores valores foram observados a 10 °C no TGO em todos os dias de análise e em D0 à temperatura de 17 °C. O diluente TRIS + gema de ovo mostrou-se como uma alternativa para conservação do sêmen suíno a 10 °C, assim como o LPD. Além disso, esses mesmos diluentes constituem alternativas para conservação a curto prazo a 17 °C.
The use of suitable extenders is important to artificial insemination success. Therefore, the objective of this study was to evaluate the efficiency of extenders at different temperatures. The following extenders were used: Beltsville Thawing Solution (BTS); TRIS (Tris-hidroximetil-aminometano - H2NC(CH2OH)3); TRIS + egg yolk (TGO), and skim powdered milk (SPM). Fifty ejaculates were analyzed regarding sperm vigor, motility, membrane functionality, and mitochondrial activity. The TGO and SPM extenders maintained the highest values for vigor and motility at 10 °C, in comparison to the other treatments (p<0.05). At 17 °C, these extenders showed better results of vigor and motility compared to the others, only until D1 (p<0.05). From D2, BTS proved to be the best extender to preserve these characteristics. A higher percentage of sperm with a functional membrane was observed for TGO at 10 °C, followed by SPM, BTS, and TRIS (p<0.05). At 17 °C, BTS maintained this characteristic, except for DO, which showed better results for TGO and SPM. Regarding the mitochondrial activity, higher values were observed at 10 °C for TGO on all days of analysis and D0 at a temperature of 17 °C. The extender TRIS + egg yolk was shown as an alternative for the conservation of swine semen at 10 °C, as well as the SPM. In addition, these same extenders are alternatives for short-term conservation at 17 °C.
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Animales , Masculino , Preservación de Semen/métodos , Porcinos , Trometamina/uso terapéutico , Yema de Huevo , Análisis de Semen/veterinariaRESUMEN
OBJECTIVE: Ischemia/reperfusion (I/R) may cause irreversible damage to tissues and organs. We evaluated the effects of dexketoprofen on a renal I/R model in rats. METHODS: The study included 30 male rats. Control group received 1 mL of saline. Dexketoprofen group received 1 mL (25 mg) of dexketoprofen intraperitoneally. After 60 minutes renal ischemia, 23 hours reperfusion was applied. In Sham group, laparotomy was performed with a medial line incision without any additional procedure. Changes in the plasma malondialdehyde (MDA), renal tissue MDA, plasma glutathione peroxidase (GPx), superoxide dismutase (SOD), catalase (CAT), BUN, creatinine and albumin levels, and histopathological changes were evaluated. RESULTS: CAT values were significantly lower in Control as compared with the Sham group. Plasma levels of MDA in the Control group were significantly higher than in the Dexketoprofen group. BUN and creatinine values were significantly higher in the Dexketoprofen group. The severity of tissue injury in the Dexketoprofen group was significantly higher than in Control and Sham groups CONCLUSION: Although dexketoprofen reduces the I/R-induced systemic inflammation, it increases renal tissue damage.
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Daño por Reperfusión , Animales , Creatinina/farmacología , Humanos , Cetoprofeno/análogos & derivados , Riñón , Masculino , Malondialdehído , Ratas , Ratas Wistar , Daño por Reperfusión/prevención & control , TrometaminaRESUMEN
ABSTRACT: The second of a two-part series, this article describes eight recently approved drugs, including the first drug approved for the treatment of SARS-CoV-2, a first-in-class HIV attachment inhibitor, and a new intravenous injection indicated for the treatment of acute pain in adults for whom other treatments are ineffective.
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Aprobación de Drogas , Adenosina Monofosfato/análogos & derivados , Adenosina Monofosfato/uso terapéutico , Alanina/análogos & derivados , Alanina/uso terapéutico , Amisulprida/uso terapéutico , Carbamatos/uso terapéutico , Cefalosporinas/uso terapéutico , Clorofenoles/uso terapéutico , Combinación de Medicamentos , Fumaratos/uso terapéutico , Humanos , Indanos/uso terapéutico , Organofosfatos/uso terapéutico , Oxadiazoles/uso terapéutico , Piperazinas/uso terapéutico , Compuestos de Espiro/uso terapéutico , Tetrazoles/uso terapéutico , Tiofenos/uso terapéutico , Trometamina/uso terapéutico , Estados Unidos , United States Food and Drug Administration , Tratamiento Farmacológico de COVID-19 , CefiderocolRESUMEN
This study presented for the first time the development and validation of a sensitive method for quantification of dopamine, noradrenaline, and adrenaline in Krebs-Henseleit solution by LC-tandem mass spectrometry. Aliquots of 2.0 mL calibrators, quality controls, and samples of Krebs-Henseleit solution incubated with tortoise's aortic ring for 30 min were extracted by solid-phase extraction. Catecholamine separation was achieved on a 100 × 4.6 mm LiChrospher RP-8 column and the quantification was performed by a mass spectrometer equipped with an electrospray interface operating in positive ion mode. The run time was 4 min and the calibration curve was linear over the range of 0.1-20.0 ng/mL. The method was applied to the measurement of basal release of dopamine, noradrenaline, and adrenaline from the tortoise Chelonoidis carbonaria aortae in vitro. One aortic ring (30 mm) per tortoise (n = 5) was incubated for 30 min in a 5 mL organ bath filled with Krebs-Henseleit solution. The method demonstrated sensitivity, precision, and accuracy enough for its application in the measurement of basal release of these catecholamines from C. carbonaria aortic rings in vitro. The mean (standard deviation) concentrations of dopamine, noradrenaline, and adrenaline were 3.48 (2.55) ng/mL, 1.40 (0.57) ng/mL, and 1.87 (1.09) ng/mL, respectively.
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Aorta/metabolismo , Monoaminas Biogénicas , Cromatografía Liquida/métodos , Espectrometría de Masas en Tándem/métodos , Animales , Monoaminas Biogénicas/análisis , Monoaminas Biogénicas/metabolismo , Monoaminas Biogénicas/farmacocinética , Células Cultivadas , Femenino , Glucosa/química , Modelos Lineales , Masculino , Arteria Pulmonar/citología , Arteria Pulmonar/metabolismo , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Porcinos , Trometamina/química , Tortugas/metabolismoRESUMEN
The purpose of this study was to evaluate the antinociceptive interaction between dexketoprofen and tapentadol in three different dose ratios, as well as the ulcerogenic activity of this combination. Dose-response curves were carried out for dexketoprofen, tapentadol, and dexketoprofen-tapentadol combinations in the acetic acid-induced writhing test in mice. On the other hand, the gastric damage of all treatments was assessed after the surgical extraction of the stomachs. Intraperitoneal administration of dexketoprofen and tapentadol induced a dose-dependent antinociceptive effect, reaching a maximal effect of about 58% and 99%, respectively. Isobolographic analysis and the interaction index showed that the three proportions produced an analgesic potentiation (synergistic interaction). Interestingly, the 1:1 and 1:3 ratios of the drugs combination produced minor gastric injury in comparison with the 3:1 proportion. Our data suggest that all proportions of the dexketoprofen-tapentadol combination produced a synergistic interaction in the acetic acid-induced visceral pain model in mice with a low incidence of gastric injury.
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Analgésicos/farmacología , Cetoprofeno/análogos & derivados , Dolor Nociceptivo/prevención & control , Tapentadol/farmacología , Trometamina/farmacología , Analgésicos/administración & dosificación , Analgésicos/efectos adversos , Animales , Relación Dosis-Respuesta a Droga , Combinación de Medicamentos , Sinergismo Farmacológico , Cetoprofeno/administración & dosificación , Cetoprofeno/efectos adversos , Cetoprofeno/farmacología , Masculino , Ratones , Ratones Endogámicos BALB C , Dimensión del Dolor , Úlcera Gástrica/inducido químicamente , Tapentadol/administración & dosificación , Tapentadol/efectos adversos , Trometamina/administración & dosificación , Trometamina/efectos adversosRESUMEN
Various animal models, especially rodents, are used to study pain, due to the difficulty of studying it in humans. Many drugs that produce analgesia have been studied and there is evidence among which NSAIDs deserve to be highlighted. Dexketoprofen (DEX) provides a broad antinociceptive profile in different types of pain; therefore, this study was designed to evaluate the profile of antinociceptive potency in mice. Analgesic activity was evaluated using the acetic acid abdominal constriction test (writhing test), a chemical model of visceral pain. Dose-response curves for i.p. DEX administration (1, 3, 10, 30 and 100 mg/kg), using at least six mice in each of at least five doses, was obtained before and 30 min after pre-treatment with different pharmacological agents. Pretreatment of the mice with opioid receptor antagonists was not effective; however, the serotonin receptor antagonist and nitric oxide synthase inhibitor produce a significant increase in DEX-induced antinociception. The data from the present study shows that DEX produces antinociception in the chemical twisting test of mice, which is explained with difficulty by the simple inhibition of COX. This effect appears to be mediated by other mechanisms in which the contribution of the NO and 5-HT pathways has an important effect on DEXinduced antinociception.
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Cetoprofeno/análogos & derivados , Receptores Opioides/genética , Receptores de Serotonina/genética , Trometamina/farmacología , Dolor Visceral/tratamiento farmacológico , Ácido Acético/farmacología , Analgesia/métodos , Analgésicos/farmacología , Animales , Antiinflamatorios no Esteroideos/farmacología , Relación Dosis-Respuesta a Droga , Humanos , Cetoprofeno/farmacología , Ratones , Antagonistas de Narcóticos/farmacología , Óxido Nítrico/genética , Serotonina/genética , Antagonistas de la Serotonina/farmacología , Dolor Visceral/genética , Dolor Visceral/patologíaRESUMEN
Due to the global decrease in jaguar population, conservation strategies are essential and the development of effective semen cryopreservation protocols would contribute to the formation of germplasm banks. Therefore, the objectives were to (1) evaluate the use of TRIS and ACP-117c extenders for jaguar semen freezing, (2) describe the ultrastructural changes in sperm after cryopreservation, and (3) evaluate the binding capacity of the thawed sperm. Eight ejaculates from five mature individuals were collected by electroejaculation, extended in TRIS or a coconut based-extender (ACP-117c), and frozen in liquid nitrogen. Samples were evaluated for sperm motility, vigor, membrane functionality, mitochondrial activity, morphology (using light microscopy, scanning electron microscopy - SEM and transmission electron microscopy - TEM), sperm kinetic parameters (by computerized analysis - CASA), and sperm binding capability using an egg yolk perivitelline membrane assay. Samples preserved in TRIS presented better post-thaw motility (46.0⯱â¯7.7%) and membrane functionality (60.5⯱â¯4.2%) and higher mitochondrial activity (21.5⯱â¯3.7%) than those preserved in ACP-117c (20.9⯱â¯5.4% motile sperm; 47.1⯱â¯2.5% functional membrane; 11.8⯱â¯1.7% mitochondrial activity). Regarding ultrastructural evaluations, SEM showed that both extenders were able to preserve the superficial membrane of the sperm, but TEM revealed the occurrence of nuclear electron lucent points, especially in samples extended in ACP-117c. Additionally, TRIS also provided a higher number of sperm bound to the perivitelline membrane (29.5⯱â¯3.3%) in comparison to samples diluted in ACP-117c (18.6⯱â¯1.5%). Overall, we suggest the use of a TRIS-based extender for cryopreservation of jaguar semen.
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Crioprotectores/farmacología , Panthera/embriología , Preservación de Semen/métodos , Espermatozoides/ultraestructura , Trometamina/farmacología , Animales , Cocos/química , Criopreservación/métodos , Crioprotectores/química , Yema de Huevo/química , Congelación , Humanos , Masculino , Microscopía Electrónica de Transmisión , Semen/fisiología , Análisis de Semen , Motilidad EspermáticaRESUMEN
Dexketoprofen trometamol (DT) is an active S (+) enantiomer of ketoprofen, and a non-steroidal anti-inflammatory agent. DT has a short biological half-life and the dosing interval is quite short when there is a need to maintain the desirable effect for longer time periods. Consequently, a controlled release DT tablet was designed for oral administration aiming to minimize the number of doses and the possible side effects. Calculations of the parameters for controlled release DT tablets were shown clearly. Controlled release matrix-type tablet formulations were prepared using hydroxypropyl methylcellulose (HPMC) (low and high viscosity), Eudragit RS and Carbopol, and the effects of different polymers on DT release from the tablet formulations were investigated. The dissolution rate profiles were compared and analyzed kinetically. An Artificial Neural Network (ANN) model was developed to predict drug release and a successful model was obtained. Subsequently, an optimum formulation was selected and evaluated in terms of its analgesic and anti-inflammatory activity. Although the developed controlled release tablets did not have an initial dose, they were found to be as effective as commercially available tablets on the market. Dissolution and in vivo studies have shown that the prepared tablets were able to release DT for longer time periods, making the tablets more effective, convenient and more tolerable.
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Comprimidos/análisis , Trometamina/efectos adversos , Administración Oral , Antiinflamatorios no Esteroideos/efectos adversos , Cetoprofeno/agonistas , Dosificación/efectos adversos , Liberación de Fármacos/efectos de los fármacos , Analgésicos/farmacocinéticaRESUMEN
Objetivo Optimizar el uso de antibióticos en la profilaxis de la cistoscopia flexible estudiando los patógenos más frecuentes de nuestro entorno y eligiendo el antibiótico según sus antibiogramas. Métodos Desde Enero del 2015 hasta Noviembre del 2015, se analizaron los urinocultivos de nuestra área, se eligió el antibiótico en función a su sensibilidad frente a los patógenos más frecuentes y se comparó con un antibiótico de amplio espectro. Desde Enero del 2016 hasta Diciembre del 2016, se realizaron las cistoscopias agrupando a los pacientes en: Grupo 1: Pacientes sin profilaxis; Grupo 2: Profilaxis con Gentamicina 240 mg; Grupo 3: Profilaxis con antibiótico seleccionado. Como variables principales se definieron la presencia de bacteriuria asintomática e ITU tras la realización de la cistoscopia flexible. Resultados Se analizaron 8.530 urinocultivos y se eligió la Fosfomicina Trometamol 3 gr como profilaxis. Se realizaron 244 cistoscopias distribuidas: Grupo 1: 86 (35%); Grupo 2: 72 (30%); Grupo 3: 86 (35%). Se detectó bacteriuria asintomática postcistoscopia en 6 pacientes (2,5%) en el Grupo 1, 7 pacientes (2,9%) en el grupo 2 y 5 pacientes (2%) en el grupo 3 no presentando diferencias significativas (p 0.120). Desarrollaron ITUs postcistoscopia 1 paciente (0,4%) en el Grupo 1, 5 pacientes (2%) en el Grupo 2 y 2 pacientes (0,8%) en el Grupo 3 sin diferencias significativas (p 0.105). Conclusión La Fosfomicina es tan efectiva como la Gentamicina en la profilaxis de la cistoscopia. Para un uso correcto de los antibióticos, se recomienda el estudio de los patógenos de nuestro entorno.
Objective To optimize the use of antibiotics in the prophylaxis of flexible cystoscopy by studying the most frequent pathogens in our environment and choosing the antibiotic according to its antibiograms. Method Between January 2015 and November 2015, urine cultures were analyzed in our area, the antibiotic was chosen based on its sensitivity to the most frequent pathogens and compared with a broad spectrum antibiotic. From January 2016 to December 2016, cystoscopy was performed by grouping patients into: Group 1 - Patients without prophylaxis, Group 2 - Prophylaxis with 240 mg gentamicin, Group 3 - Selected antibiotic prophylaxis. The main variables were the presence of asymptomatic bacteriuria and UTI after flexible cystoscopy. Results 8530 urine cultures were analyzed and 3 g of fosfomycin trometamol was chosen as the prophylactic. There were 244 cystoscopies: Group 1: 86 (35%); Group 2: 72 (30%); Group 3: 86 (35%). Asymptomatic bacteriuria was detected in 6 patients (2.5%) in Group 1, 7 patients (2.9%) in Group 2 and 5 patients (2%) in Group 3, showing no significant differences (p = 0.120). Post-cystoscopic urinary tract infection developed in 1 patient (0.4%) in Group 1, 5 patients (2%) in Group 2 and 2 patients (0.8%) in Group 3, which showed no significant differences (p 0.105). Conclusion Fosfomycin is as effective as Gentamicin as a prophylactic in cystoscopy. The study of the pathogens in each environment is recommended to correctly prescribe the antibiotic.
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Humanos , Pruebas de Sensibilidad Microbiana , Cistoscopía , Antibacterianos , Bacteriuria , Triacetonamina-N-Oxil , Trometamina , Infecciones Urinarias , Gentamicinas , Profilaxis AntibióticaRESUMEN
SummaryThe aim of this study was to establish a functional freezing-thawing protocol for epididymal sperm of collared peccaries (Pecari tajacu L., 1758) by comparing different extenders. The epididymal sperm from 12 sexually mature males was recovered by retrograde flushing using Tris-based or coconut water-based (ACP®-116c) extenders. After initial evaluation, samples were diluted and frozen with the same extenders to which 20% egg yolk and 6% glycerol were added. After 2 weeks, thawing was performed at 37°C/60 s and sperm motility, vigour, morphology, functional membrane integrity, sperm viability, sperm plasma membrane integrity, and a computer-assisted semen analysis (CASA) were assessed. In addition, to evaluate the survival of frozen-thawed sperm, a thermal resistance test (TRT) was executed. Samples preserved using Tris were in better condition compared with those preserved using ACP®, showing higher values for most assessments performed, including CASA and the TRT (P<0.05). After determining Tris to be the better of the two extenders, additional samples were thawed using different thawing rates (37°C/60 s, 55°C/7 s, 70°C/8 s). Sperm thawed at 37°C/60 s had the greatest preservation (P<0.05) of viability (54.1 ± 5.9%) and functional membrane integrity (43.2 ± 5.4%), and had higher values for various CASA parameters. In conclusion, we suggest the use of a Tris-based extender added to egg yolk and glycerol for the cryopreservation of epididymal sperm obtained from collared peccaries. In order to achieve better post-thawing sperm quality, we suggest that samples should be thawed at 37°C/60 s.
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Cocos/química , Criopreservación/veterinaria , Crioprotectores/farmacología , Epidídimo/fisiología , Extractos Vegetales/farmacología , Espermatozoides/fisiología , Trometamina/farmacología , Animales , Artiodáctilos , Criopreservación/métodos , Epidídimo/efectos de los fármacos , Masculino , Análisis de Semen , Espermatozoides/efectos de los fármacosRESUMEN
A cocrystal of glibenclamide, an antidiabetic drug classified as type II compound according to the Biopharmaceutics Classification System, has been synthesized using tromethamine as coformer in 1:1 molar ratio, by slow solvent evaporation cocrystalization. The cocrystal obtained was characterized by X-ray powder diffraction, differential scanning calorimetry, Raman, mid infrared, and near-infrared spectroscopy. The results consistently show the formation of a cocrystal between active pharmaceutical ingredients and conformer with the synthons corresponding to hydrogen bonding between hydrogen in amines of tromethamine and carbonyl and sulfonyl groups in glibenclamide.
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Cristalización/métodos , Excipientes/química , Gliburida/química , Hipoglucemiantes/química , Trometamina/química , Rastreo Diferencial de Calorimetría , Enlace de Hidrógeno , Difracción de Polvo , Solubilidad , Espectroscopía Infrarroja por Transformada de Fourier , Espectrometría Raman , Difracción de Rayos XRESUMEN
This review presents the most relevant investigations concerning the biocatalytic kinetic resolution of racemic ketoprofen to dexketoprofen for the last 22 years. The advantages related to the administration of the dex-enantiomer in terms of human health, the so called "chiral switch" in the pharmaceutical industry and the sustainability of biotransformations have been the driving forces to develop innovative technology to obtain dexketoprofen. In particular, the kinetic resolution of racemic ketoprofen through enantiomeric esterification and hydrolysis using lipases as biocatalysts are thoroughly revised and commented upon. In this context, the biocatalysts, acyl-acceptors (alcohols), reaction conditions, conversion, enantiomeric excess, and enantiomeric ratio among others are discussed. Moreover, the investigations concerning scaling up processes in order to obtain an optically pure enantiomer of the profen are presented. Finally, some guidelines about perspectives of the technology and research opportunities are given.
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Cetoprofeno/análogos & derivados , Trometamina , Biocatálisis , Química Farmacéutica , Esterificación , Humanos , Hidrólisis , Cetoprofeno/química , Cetoprofeno/metabolismo , Cinética , Lipasa , Estereoisomerismo , Trometamina/química , Trometamina/metabolismoRESUMEN
The adsorption of human immunoglobulin G (IgG) and human serum albumin (HSA) on a non-calcined Mg-Al layered double hydroxide (3:1 Mg-Al LDH) was studied in batch and fixed bed experiments, focusing on the effect of buffer solution and pH over sorbent uptake. Mg-Al LDH was synthesized and characterized by X-ray diffraction (XRD), N2 adsorption-desorption isotherms at -196°C, X-ray photoelectron spectroscopy (XPS), Zero point charge (pHzpc), particle size distribution and Fourier transform infra-red (FTIR). Batch adsorption experiments were performed in order to investigate the effects of pH on IgG and HSA adsorption with different buffers: sodium acetate (ACETATE), sodium phosphate (PHOSPHATE), 3-(N-morpholino) propanesulfonic acid (MOPS), 4-(2-Hydroxyethyl)piperazine-1-ethanesulfonic acid (HEPES) and trizma-hydrochloric acid (TRIS-HCl). Maximum adsorption capacities estimated by the Langmuir model were 239mgg-1 for IgG and 105mgg-1 for HSA in TRIS-HCl buffer. On the other hand, the highest selectivity for IgG adsorption over HSA was obtained with buffer PHOSPHATE (pH 6.5). The maximum IgG and HSA adsorption uptake in this case were 165 and 36mgg-1, respectively. Fixed bed experiments were carried out with both proteins using PHOSPHATE buffer (pH 6.5), which confirmed that IgG was more selectively adsorbed than HSA on Mg-Al LDH and both could be fully recovered by elution with sodium chloride (NaCl).
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Compuestos de Aluminio/química , Inmunoglobulina G/química , Compuestos de Magnesio/química , Albúmina Sérica Humana/química , Agua/química , Adsorción , Tampones (Química) , HEPES/química , Humanos , Concentración de Iones de Hidrógeno , Cinética , Morfolinas/química , Fosfatos/química , Acetato de Sodio/química , Soluciones , Trometamina/químicaRESUMEN
ABSTRACT Drug delivery to treat ocular disorders locally is a challenging endeavor. Traditional ocular dosage form - eye drops - exhibits poor availability, consequently inefficient therapeutic response. The objective of the study was to formulate and characterize a ketorolac tromethamine ocular system with a prolonged release pattern based on liposomes as a vesicular carrier and to design once daily liquid preparation realizing the thermal in situ gelation principle. Liposomes were prepared by film hydration method. The influence of cholesterol concentration, pH and volume of hydration medium, and type and concentration of charging imparting agents were studied. Liposomes were characterized via, morphological examination, vesicular size, and encapsulation efficiency, and in vitro release performance, moreover its stability was assessed. The results obtained highlighted that liposomes showed a closed vesicular multi-lamellar structure. Ketorolac was successfully encapsulated within the liposomal structure in a cholesterol and charge inducing agent concentration-dependent behaviour. The dispersion of liposomes within thermosensitive Poloxamer in situ gel was able to retard the release of the drug by diffusion providing a controlled prolonged delivery. The liposomal formulations were physically stable for six months. Ketorolac tromethamine in situ liposomal gel representing an efficient alternative in terms of ocular retention and patient compliance when compared with conventional eye drops.
Asunto(s)
Ketorolaco Trometamina/farmacocinética , Reactividad-Estabilidad , Composición de Medicamentos/clasificación , Liposomas/antagonistas & inhibidores , Trometamina/antagonistas & inhibidores , Anomalías del Ojo/complicaciones , Enfermedades Cutáneas Vesiculoampollosas , Administración OftálmicaRESUMEN
BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs) are the most common type of medication used in the treatment of acute pain. Ketorolac trometamol (KT) is a nonnarcotic, peripherally acting nonsteroidal anti-inflammatory drug with analgesic effects comparable to certain opioids. OBJECTIVE: The aim of this study was to compare the efficacy of KT and naproxen (NA) in the treatment of acute low back pain (LBP) of moderate-to-severe intensity. PATIENTS AND METHODS: In this 10-day, Phase III, randomized, double-blind, double-dummy, noninferiority trial, participants with acute LBP of moderate-to-severe intensity as determined through a visual analog scale (VAS) were randomly assigned in a 1:1 ratio to receive sublingual KT 10 mg three times daily or oral NA 250 mg three times daily. From the second to the fifth day of treatment, if patient had VAS >40 mm, increased dosage to four times per day was allowed. The primary end point was the reduction in LBP as measured by VAS. We also performed a post hoc superiority analysis. RESULTS: KT was not inferior to NA for the reduction in LBP over 5 days of use as measured by VAS scores (P=0.608 for equality of variance; P=0.321 for equality of means) and by the Roland-Morris Disability Questionnaire (P=0.180 for equality of variance test; P=0.446 for equality of means) using 95% confidence intervals. The percentage of participants with improved pain relief 60 minutes after receiving the first dose was higher in the KT group (24.2%) than in the NA group (6.5%; P=0.049). The most common adverse effects were heartburn, nausea, and vomiting. CONCLUSION: KT is not inferior in efficacy and delivers faster pain relief than NA.
Asunto(s)
Ketorolaco/administración & dosificación , Dolor de la Región Lumbar/tratamiento farmacológico , Naproxeno/administración & dosificación , Trometamina/administración & dosificación , Antiinflamatorios no Esteroideos/administración & dosificación , Antiinflamatorios no Esteroideos/química , Antiinflamatorios no Esteroideos/metabolismo , Método Doble Ciego , Humanos , Ketorolaco/química , Ketorolaco/metabolismo , Naproxeno/química , Naproxeno/metabolismo , Trometamina/química , Trometamina/metabolismoRESUMEN
The aim of this study was to compare the efficacy of preoperative and postoperative dexketoprofen trometamol for pain control after third molar surgery. Sixty subjects indicated for impacted mandibular third molar surgery were randomly assigned to two groups: preoperative (group 1, n = 30) and postoperative (group 2, n = 30) administration. Group 1 received 25 mg of dexketoprofen trometamol 30 min before surgery and 1 placebo capsule (same color and size with active drug) immediately after surgery. Group 2 received the placebo capsule 30 min before surgery and 25 mg of dexketoprofen trometamol immediately after surgery. Pain intensity was assessed using a numeric rating scale (NRS) during the first 8 h. The time of the need for a second dose of dexketoprofen trometamol, after the first administration, was recorded. The data were analyzed using mixed-model repeated-measures (MMRM), Wilcoxon rank-sum, and Kaplan-Meier analysis. After the 8 h period, no statistically significant difference was observed in the intensity of pain (MMRM, p = 0.41); and no significant difference in the time for a second dose (p = 0.956). In conclusion, preoperative administration of dexketoprofen trometamol is a reasonable clinical approach that is as effective as conventional postoperative pharmacological treatment, with the advantage of allowing early analgesia before pain develops. (ClinicalTrials.gov: NCT02380001).
Asunto(s)
Antiinflamatorios no Esteroideos/administración & dosificación , Cetoprofeno/análogos & derivados , Tercer Molar/cirugía , Dolor Postoperatorio/prevención & control , Trometamina/administración & dosificación , Adolescente , Adulto , Método Doble Ciego , Femenino , Humanos , Cetoprofeno/administración & dosificación , Masculino , Manejo del Dolor , Dimensión del Dolor , Estudios Prospectivos , Extracción Dental , Resultado del TratamientoRESUMEN
PURPOSE: To evaluate whether post-hemorrhagic shock mesenteric lymph (PSML) is involved in cardiac dysfunction induced by hemorrhagic shock. METHODS: The hemorrhagic shock model (40±2 mmHg, 3h) was established in rats of the shock and shock+drainage groups; and PSML drainage was performed from hypotension 1-3h in the shock+drainage rats. Then, the isolated hearts were obtained from the rats for the examination of cardiac function with Langendorff system. Subsequently, the isolated hearts were obtained from normal rats and perfused with PSML or Krebs-Henseleit solution, and the changes of cardiac function were observed. RESULTS: The left ventricular systolic pressure (LVSP) and the maximal rates of LV developed pressure (LVDP) rise and fall (±dP/dt max) in the shock and shock+drainage groups were lower than that of the sham group; otherwise, these indices in the shock+drainage group were higher compared to the shock group. In addition, after isolated hearts obtained from normal rats perfusing with PSML, these cardiac function indices were gradual decline along with the extension of time, such as heart rate, LVSP, ±dP/dt max, etc. CONCLUSION: Post-hemorrhagic shock mesenteric lymph is an important contributor to cardiac dysfunction following hemorrhagic shock.
Asunto(s)
Cardiopatías/etiología , Cardiopatías/fisiopatología , Linfa/fisiología , Mesenterio/fisiopatología , Choque Hemorrágico/complicaciones , Choque Hemorrágico/fisiopatología , Animales , Modelos Animales de Enfermedad , Drenaje/métodos , Glucosa , Frecuencia Cardíaca/fisiología , Ventrículos Cardíacos/fisiopatología , Masculino , Mesenterio/patología , Distribución Aleatoria , Ratas Wistar , Valores de Referencia , Factores de Tiempo , Trometamina , Presión Ventricular/fisiologíaRESUMEN
PURPOSE: To evaluate whether post-hemorrhagic shock mesenteric lymph (PSML) is involved in cardiac dysfunction induced by hemorrhagic shock. METHODS: The hemorrhagic shock model (40±2 mmHg, 3h) was established in rats of the shock and shock+drainage groups; and PSML drainage was performed from hypotension 1-3h in the shock+drainage rats. Then, the isolated hearts were obtained from the rats for the examination of cardiac function with Langendorff system. Subsequently, the isolated hearts were obtained from normal rats and perfused with PSML or Krebs-Henseleit solution, and the changes of cardiac function were observed. RESULTS: The left ventricular systolic pressure (LVSP) and the maximal rates of LV developed pressure (LVDP) rise and fall (±dP/dt max) in the shock and shock+drainage groups were lower than that of the sham group; otherwise, these indices in the shock+drainage group were higher compared to the shock group. In addition, after isolated hearts obtained from normal rats perfusing with PSML, these cardiac function indices were gradual decline along with the extension of time, such as heart rate, LVSP, ±dP/dt max, etc. CONCLUSION: Post-hemorrhagic shock mesenteric lymph is an important contributor to cardiac dysfunction following hemorrhagic shock. .