Dexketoprofen más pamabrom versus acetaminofen en dismenorrea primaria: estudio controlado, randomizado, doble ciego, multicéntrico / Dexketoprofen plus pamabrom versus acetaminophen in primary dysmenorrhea: a controlled, randomized, double-blind, multicenter study

RESUMEN Introducción: se sabe que las concentraciones plasmáticas de hormona antidiurética o vasopresina son más altas en las mujeres con dismenorrea primaria (DiPr) y podría ser causa de retención de agua con signos y síntomas concomitantes que agravan su cuadro clínico. La monoterapia con AINEs en ocasiones alcanza solo un alivio parcial porque no incide sobre la vasopresina. Objetivo: evaluar la eficacia y tolerabilidad del dexketoprofeno + pamabrom en la DiPr tomando como referencia el acetaminofén. Materiales y métodos: estudio doble ciego, controlado, randomizado, en pacientes con DiPr asignados al azar. Fueron aleatorizadas 172 pacientes, 86 en cada grupo 1) Grupo casos (DP): dexketoprofeno + pamabrom o 2) Grupo control (AC): acetaminofén. Se evaluó la evolución de la intensidad del dolor, el alivio del dolor, la gravedad de otros síntomas presentes y la satisfacción global del médico y paciente. Se registró las reacciones adversas. Resultados: la disminución de la intensidad del dolor, de los síntomas acompañantes y el alivio del dolor evaluados por la EVA, la PID, la SPID, el PAR y el TOTPAR respectivamente es mayor y más rápida de modo significativo en todos los tiempos para la combinación DP. Las reacciones adversas fueron mínimas. La satisfacción global de pacientes y médicos respecto al tratamiento es significativa a favor de la combinación DP. Conclusiones: dexketoprofeno + pamabrom es significativamente más eficaz y rápido en el control del dolor y otros síntomas presentes en la dismenorrea primaria que acetaminofén demostrando la validez de añadir un diurético suave a un AINE para incrementar su eficacia. El tratamiento DP es bien tolerado (AU).

ABSTRACT Background: It is known that plasma concentrations of antidiuretic hormone or vasopressin are higher in women with primary dysmenorrhea (DiPr) and could cause water retention with concomitant signs and symptoms that aggravate the illness. Monotherapy with NSAIDs sometimes achieves only partial relief because it does not affect vasopressin. Objective: The aim was to evaluate the efficacy and tolerability of dexketoprofen + pamabrom in DiPr taking as reference acetaminophen. Materials and methods: Double-blind, controlled, randomized study in patients with DiPr random to 1) Case group (PD): dexketoprofen + pamabrom or 2) Control group (CA): acetaminophen. The evolution of pain intensity, pain relief, severity of other present symptoms and overall satisfaction of the doctor and patient were evaluated. Adverse reactions were recorded. Results: 172 patients were randomized, 86 in each group. The decrease in pain intensity, accompanying symptoms and pain relief evaluated by VAS, PID, SPID, PAR and TOTPAR respectively is significantly greater and faster at all times for the combination DP. Adverse reactions were minimal. The overall satisfaction of patients and doctors regarding treatment is significant in favor of the DP combination. Conclusions: Dexketoprofen + pamabrom is significantly more effective and faster in the control of pain and other symptoms present in primary dysmenorrhea than acetaminophen demonstrating the validity of adding a mild diuretic to an NSAID to increase its effectiveness. DP treatment is well tolerated (AU).

Receptors involved in dexketoprofen analgesia in murine visceral pain

Various animal models, especially rodents, are used to study pain, due to the difficulty of studying it inhumans. Many drugs that produce analgesia have been studied and there is evidence among whichNSAIDs deserve to be highlighted. Dexketoprofen (DEX) provides a broad antinociceptive profile indifferent types of pain; therefore, this study was designed to evaluate the profile of antinociceptivepotency 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 and30 min after pre-treatment with different pharmacological agents. Pretreatment of the mice with opioidreceptor antagonists was not effective; however, the serotonin receptor antagonist and nitric oxidesynthase inhibitor produce a significant increase in DEX-induced antinociception. The data from thepresent study shows that DEX produces antinociception in the chemical twisting test of mice, which isexplained with difficulty by the simple inhibition of COX. This effect appears to be mediated by othermechanisms in which the contribution of the NO and 5-HT pathways has an important effect on DEXinduced antinociception.

Development and validation of highly selective method for the determination of imatinib mesylate and dexketoprofen trometamol combination in three different media

Imatinib mesylate is a small molecule used in cancer therapy as a thyrosine kinase inhibitor. Dexketoprofen trometamol is a non-steroidal anti-inflammatory drug that has seen use in cancer therapy in combination with an anticancer drug to minimize tumor size and to reduce pain in patients. In the present study, imatinib mesylate and dexketoprofen trometamol were selected as potential model drugs to be used in combination. A new, simple and selective Ultra Performance Liquid Chromatography method was developed and validated to determine the drug substances in distilled water, in a pH 7.4 phosphate buffer and in Dulbecco's Modified Eagle Medium. The proposed method was developed using a BEH C-18 column with isocratic elution. A mixture of methanol:acetonitrile (80:20, v/v) and pH 9.5, 0.05 M ammonium acetate were (70:30, v/v) used as a mobile phase. Detection was carried out with a flow rate of 0.3 mL/min, a column temperature of 30°C and an injection volume of 20 µL. The method was validated considering linearity, accuracy, precision, specificity, robustness, detection limit and quantitation limit values, and was found to be linear in a range from 0.05 to 20.0 µg/mL for the three different media

Development of controlled release dexketoprofen tablets and prediction of drug release using Artificial Neural Network (ANN) modelling

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.

Diclofenac versus combination of dexketoprofen and hyoscine N-butyl bromide in the treatment of renal colic in the emergency room setting: A single-blinded randomized controlled trial in a tertiary government hospital in the Philippines

INTRODUCTION@#Renal colic pain is a very severe pain usually being consulted at the emergency room.New pain relievers together with combination of other drugs is used for symptomatic relief. Thisstudy compared the efficacy and tolerability of Diclofenac versus Dexketoprofen with Hyoscine N-butyl bromide (HNBB) in the management of acute renal colic at the emergency room.@*METHODOLOGY@#This was a single blind, randomized prospective study done from June 1, 2017 toAugust 31, 2017 at the emergency department of the Jose Reyes Memorial Medical Center. Allocationand randomization were done into two treatment groups: the Diclofenac and Dexketoprofen + HNBB.Subjectivity of pain relief was based using visual analogue score (VAS), this was taken before thetreatment and 15, 30 and 60 minutes after administration of treatment.@*RESULTS@#Twenty nine (29) patients were grouped into two: Dicloenac group (n=15) and Dexketoprophen+ HNBB group (n= 14). Pain reduction in the combination group had a faster pain relief compared toDiclofenac alone with a 41% and 17% decline, respectively. The study showed that a faster pain reliefwas achieved with the Dexkoprophen + HNBB combination compared to Diclofenac alone.@*CONCLUSION@#Timing and onset of pain control in patients presenting with renal colic pain is essentialin the emergency room setting to provide adequate relief. The use of the combination therapy ofDexkotoprofen + HNNB may have a significant advantage in terms of rapid onset of relief.

Antinociceptive local effect of the combination of dexketoprofen trometamol and chlorhexidine gluconate in a formalin test: an additive effect

ABSTRACT A drug delivery system (DDS) with analgesic and antibacterial properties would be desirable for the local control of post-operatory pain and the prevention for surgical site infection (SSI). The objective of the present study was to evaluate the antinociceptive effect of the combination between dexketoprofen trometamol (DXT) and chlorhexidine gluconate (CHX) in the formalin pain model. Different doses of CHX were combined with DXT and were locally administered in rats paw simultaneously with 5% formalin dilution. Flinches were documented and the antinociceptive effect was calculated. The area under the curve of each experimental group were calculated and the % of antinociception were compared. The groups of CHX and DXT showed similar antinociceptive effect. The combination groups (DXT-CHX) showed higher antinociceptive effect that the one obtained with individual molecules. Besides the confirmation of DXT local antinociceptive properties, CHX also showed a positive effect; and an additive effect when combined with DXT

Preparation and in vitro Transdermal Studies of Dexketoprofen Trometamol Hydrogel Patches / 中国药师

Objective: To prepare dexketoprofen trometamol hydrogel patches, optimize the formula and evaluate in vitro transdermal properties.Methods: Dexketoprofen trometamol hydrogel patches were prepared with NP-800 as the hydrogel patch carrier, aluminum hydrochloride as the crosslinking agent, EDTA as the crosslinking modifier and glycerol as the moisturizing agent.The formula was screened by orthogonal design with the initial viscosity, holding force, peel strength and 12 h cumulative transdermal quantity as the evaluation indices to screen out the best formula.The transdermal absorption test was carried out with an improved Franz diffusion cells to compare the enhancement of Aznoe, oleic acid and menthanol on dexketoprofen trometamol hydrogel patches.Results: The best formula was as follows: the mass percentage of NP-800, glycerol, glycerol and EDTA was 5%, 0.3% , 25% and 0.15% , respectively.The transdermal enhancers had transdermal enhancement on dexketoprofen trometamol, and among them, 3% Azone had the most significant enhancement with the enhancing rate of 3.26.Conclusion: The preparation and formula of dextroxyprofen trometamol hydrogel patches are stable, reasonable and feasible.

Effect of paracetamol, dexketoprofen trometamol, lidocaine spray, pethidine & diclofenac sodium application for pain relief during fractional curettage: A randomized controlled trial.

Background & objectives: Patients frequently experience pain of moderate to severe degree during gynaecologic procedures. This prospective, randomized, placebo-controlled trial was aimed to investigate the analgesic efficacy of preoperative oral dexketoprofen trometamol, intravenous paracetamol, lidocaine spray, pethidine and diclofenac sodium on fractional curettage procedure. Methods: A total of 144 mutiparous women were randomly allocated to one of the six groups. The first group (control group) consisted of 22 participants and they did not receive any treatment. The second group had 26 participants receiving oral 25 mg dexketoprofen trometamol. The 23 participants of the third group received two puff lidocaine sprays on cervical mucosa. The forth group consisted of 25 participants receiving 100 mg pethidine. In the fifth group, the 23 participants received 1000 mg intravenous paracetamol and the sixth group consisted of 25 participants receiving diclofenac sodium. Results: Pethidine was the best choice for reducing pain score during curettage procedure (t2:intra-operative). All analgesic procedures were significantly effective in reducing pain during postoperative period (t3). Significant pain reduction was achieved for both intra- and postoperative period by using analgesics. Interpretation & conclusions: The results of our study showed that lidocaine puffs provided the best pain relief than the other analgesics used. Therefore, lidocaine may be considered as the first choice analgesic in fractional curettage (NCT ID: 01993589).

Intra-articular injection of dexketoprofen in rat knee joint : Histopathologic assessment of cartilage & synovium.

Background & objectives: Effective pain control following outpatient surgical procedures is an important aspect of patient discharge. This study was carried out with an aim to investigate the histopathological effects of intra-articular dexketoprofen trometamol injection in knee joint on synovium and cartilage in an experimental rat model. Methods: In each of 40 rats, the right knee was designated as the study group and the left knee as the control group (NS group). Under aseptic conditions, 35 rats received an injection of 0.25 ml (6.25 mg) dexketoprofen trometamol into the right knee joint and an injection of 0.25 ml 0.9 per cent normal saline solution into the left knee joint. On the 1st, 2nd, 7th, 14th, and 21st days after intra-articular injection, rats in specified groups were sacrificed by intraperitoneal injection of 120 mg/kg sodium thiopental. Knee joints were separated and sectioned for histopathological examination. Inflammatory changes in the joints were recorded according to a grade scale. Results: No significant difference in terms of pathological changes both in synovium and cartilage was observed between the NS group and the study group on days 1, 2, 7, 14 and 21 after intra-articular injection of dexketoprofen or saline in the knee joint. Interpretation & conclusions: The findings showed no evidence of significant histopathological damage to the cartilage and synovia for a period up to 21 days following intra-articular administration of dexketoprofen trometamol in the knee joints of rats.

Preparation and in vtro Release of Dexketoprofen Enteric-coated Pellets / 中国药师

Objective:To prepare dexketoprofen enteric-coated pellets and explore the drug release rate respectively in 0. 1 mol· L-1 hydrochloric acid and phosphate buffered saline(PBS,pH 6. 8). Methods:Dexketoprofen enteric-coated pellets were prepared u-sing fluid-bed coating technology, the blank sugar pellets were coated with drug layer, isolation layer and enteric layer in order. Drug-loading rate as the index, the optimal concentrations of HPMC and drug were screened. Such indicators as adhesion, pellet uniform and surface color as the indices, the coating process was optimized by orthogonal experiment. Drug release in PBS of the enteric-coated pel-lets and the common enteric-coated tablets were compared. Results:The prepared pellets showed the properties of uniform drug load-ing, high drug-loading rate, complete round shape and lustrous appearance. The concentration of HPMC and drug was 5% and 15%, respectively. The optimal coating process was as follows:the material temperature was 36℃, the atomization pressure was 1. 0 bar and the airbrush rate was 0. 8 ml·min-1 . The drug release of the pellets in hydrochloric acid was below 10% in 2 hours, while the release in PBS was greater than that of the common enteric-coated tablets. Conclusion: The prepared enteric-coated pellets are feasible in technology, and exhibit satisfactory acid endurance and drug release in vitro.

Evaluation of the effects of dexketoprofen trometamol on knee joınt: an in vivo & in vitro study.

Background & objectives: Intra-articular (ia) injections of local anaesthetics and non-steroidal anti-inflammatory drugs (NSAID’s) are simple and efficient to ensure post-operative analgesia but some of these have toxic effects on the synovium and cartilage. Dexketoprofen is recently introduced S-enantiomer of ketoprofen with a better analgesic and side effect profile. This study was done to evaluate the possible toxic effects of dexketoprofen trometamol on knee joint cartilage and symovium in vitro and in vivo. Methods: Forty one Sprague-Dawley rats were anaesthetized by ketamine. Dexketoprofen trometamol (0.25 ml) was injected into the right knee joint of the 35 rats and 0.25 ml serum physiologic into the left knee joint of the same animals. Six rats were sham operated. Thirty five animals were randomly divided into five equal groups. Seven animals were sacrified at 24th, 48th hours and 7th, 14th, and 21st days of the injections. Haematoxylin eosin stained sections from the knee joints were evaluated for the signs of inflammation according to five point scale. Primary chondrocytes were isolated from the articular cartilages of rats for in vitro studies. Cells were exposed to 0.25 ml dexketoprofen trometamol or 0.25 ml dexketoprofen medium mixture at 1:1 ratio for 15, 30, 45 and 60 min. Cell viability was determined by 3-(4, 5- dimethylthiazole-2-yl)-2.5-diphenyl tetrazolium bromide (MTT) assay, 24, 48 and 72 h after drug treatment. Results: No significant histopathologic differences were found between dexketoprofen trometamol and physiologic serum (control) applied joints at all time intervals in in vivo study. Cell proliferation in dexketoprofen trometamol treated chondrocytes was inhibited for all time intervals compared to control. In dexketoprofen-medium mixture groups significant differences were only seen 24 h after the 30 and 45 min application of medium: drug mixture. Interpretation & conclusions: Intra-articular application of dexketoprofen trometamol into the rat knee joints did not cause significant histopathological changes, but its in vitro application in primary chondrocyte culture caused significant cytotoxicity. The effects of dexketoprofen at different concentrations need to be further investigated in culture of rat and human chondrocytes.

Determination of the Plasma Concentration of Dexketoprofen with HPLC in Rabbits / 中国药房

OBJECTIVE:To establish a HPLC method for determining the concentration of dexketoprofen in rabbit’s pla_ sma.METHODS:Dexketoprofen was extracted from samples with ether.HPLC was performed on C 18 column with methyl al?cohol-50mmol/L sodium dihydrogen phosphate as mobile phase.Detection wavelength was260nm.RESULTS:The linear range was0.05～25?g/ml.Recovery was99.92%～100.54%.Within-day and between-day RSDs were0.56%～2.94%and0.6%～2.89%respectively.CONCLUSION:This method is simple,accurate and good in repetitiveness.Satisfactory results have been obtained in determining plasma concentrations of dexketoprofen in6rabbits after taking dexketoprofen-?-cy?clodextrin inclusion microspheres.