Clinician's dilemma: Naproxen-induced liver injury

Naproxen is a widely used nonsteroidal anti-inflammatory drug (NSAID) in pediatric population, used for mild-to-moderate pains, arthritis, and other immune-mediated disorders. It rarely causes clinically apparent liver injury in the adult population taking high doses of the drug over a prolonged period and is reported even rarer in pediatric population. We present a case of drug-induced liver injury (DILI) in a 13-year-old girl taking naproxen in therapeutic doses for juvenile rheumatoid arthritis. There was a complete recovery of liver function following discontinuation of naproxen therapy.

A ingestão do anti-inflamatório não esteroide naproxeno afeta parâmetros neuromusculares e metabólicos? / Does the ingestion of naproxen affect neuromuscular and metabolic parameters?

O naproxeno, assim como outros anti-inflamatórios não esteroides (AINEs), está entre os medicamentos mais prescritos no mundo. O objetivo do presente estudo é analisar o efeito da ingestão de naproxeno em parâmetros neuromusculares e determinar seu efeito no dano muscular por meio do uso do marcador lactato. Metodologicamente, foi conduzido um estudo cruzado randomizado, duplo-cego e controlado por placebo em 11 homens treinados em resistência, que realizaram uma sessão de treinamento de força após ingerir 500 mg de naproxeno e outra sessão de treinamento após ingerir um placebo. Os participantes realizaram três séries de supino horizontal com uma carga de 90% da repetição máxima (1RM) até a falha concêntrica. As variáveis de resultado incluíram número de repetições, carga de trabalho e lactato. Os resultados mostraram que há uma correlação positiva e moderada entre as variáveis somatório de repetições e carga total e entre as variáveis lactato e carga total, no grupo naproxeno. No grupo placebo, a correlação positiva e moderada deu-se entre somatório de repetições e carga total. Na análise magnitude baseada nas interferências, as variáveis se mostraram possíveis para uma probabilidade positiva ou trivial e improvável para uma probabilidade negativa. Concluiu-se no presente estudo que o uso do naproxeno como recurso ergogênico no treinamento de força reduz a percepção de fadiga, mas não tem efeito direto no dano muscular, analisado a partir do marcador lactato, logo não interfere de maneira significativa nos parâmetros neuromusculares analisados.

Naproxen, as other non-steroidal anti-inflammatory drugs (NSAIDs), features among the most widely prescribed drugs in the world. The aim of this study is to analyze the effect of naproxen intake on neuromuscular parameters and determine its effect on muscle damage through the use of the lactate marker. In terms of methodology, a randomized, double-blind, placebo-controlled crossover study was conducted on 11 resistance-trained men who underwent a strength training session after taking 500 mg of naproxen and another training session after taking a placebo. The participants performed three sets of horizontal bench presses with a load of 90% maximum repetition (1RM) until concentric failure. Result variables included number of repetitions, workload and lactate. The results showed that there is a positive and moderate correlation between the sum of repetition and total load variables and between lactate and total load variables in the naproxen group. In the placebo group, a positive and moderate correlation was observed between sum of repetitions and total load. In the magnitude analysis, based on the interferences, the variables were shown to be possible for a positive or trivial probability and unlikely for a negative probability. It was concluded that the use of naproxen as an ergogenic resource in strength training reduces the perception of fatigue but has no direct effect on muscle damage when analyzed from the lactate marker, therefore it does not significantly interfere in the analyzed neuromuscular parameters.

Evaluation genotoxicity of acetylnerolin based on quantitative structure-activity relationship model and in vitro tests / 中国药理学与毒理学杂志

OBJECTIVE To evaluate the genotoxicity of naproxen (NPX) impurities acetylnerolin (Ace). METHODS The genotoxicity of Ace was predicted by ADMET, Derek and Sarah with the quanti?tative structure-activity relationship (QSAR). The chromosomal aberration and bacterial reverse-muta?tion (Ames) tests were performed to verify the above results. In chromosomal aberration tests, CHL cells were incubated with Ace 10, 20 and 40 mg · L-1 for 4 h in the presence or absence of metabolic activation system solution (S9 mix). Methyl methane sulfonate (MMS) 20 mL · L-1 without S9 mix and cyclophosphamide (CP) 12 mg · L-1 with S9 mix served as positive control. The number of chromo?somes in each aberrant metaphase (including fissure, exchange, ring, break and polyploid) was counted and recorded, when the distortion rate less than 5％was considered negative and more than 10％was considered positive. In Ames test, the potential mutagenicity was evaluated using five strains of S. typhimurium ( TA97,TA98,TA100,TA102 and TA1535). They were treated with Ace 5, 25, 125 and 625μg per plate with or without S9 mix and incubated for 48-72 h. When without S9 mix, Dexon 50μg per plate served as positive control for TA97 and TA98, MMS 2.0μL per plate served as positive control for TA100 and TA102, and sodium azide 1.5μg per plate served as positive control for TA1535. When with S9 mix, 2-AF 100 μg per plate served as positive control for TA97, TA98 and TA100, 1, 8-dihydroxyanthraquinone (100μg per plate) served as positive control for TA102 and CP 50μg per plate served as positive control for TA1525. When the number of colonies was at least two-fold that of the negative control, the compound was considered mutagenic. RESULTS Although the Derek and Sarah software predicted that the NPX impurities were not genotoxic, ADMET data showed that Ace could induce chromosomal aberrations. The distortion rate of Ace 40 mg · L-1 was greater than 5％, but less than 10％. The distortion rate of Ace was less than 5％when<20 mg·L-1. Consistent with the results of ADMET, Ace might induce chromosomal aberrations. Ames test results showed that Ace did not signifi?cantly increase the number of bacteria (5-625μg per plate) compared with the negative control. Contrary to the ADMET results, Ace had no mutagenicity. CONCLUSION Ace has potential chromosomal muta?genicity. For life-long usage of NPX, the content of Ace should be reduced from 0.15％of conventional impurities to 0.015％.

Factors Affecting Quality of Life and Satisfaction in Patients with Arthritis after Change to a Fixed-Dose Naproxen/Esomeprazole Combination Drug

BACKGROUND: In drug therapy for patients with arthritis, a naproxen/esomeprazole combination drug may be a tolerable choice because it can minimize gastrointestinal and cardiovascular adverse effects. The aim of this study was to investigate the changes in quality of life (QOL), medication adherence, and satisfaction after switch from the existing drug to the combination drug. In addition, we analyzed the correlation between the above-mentioned variables and the stratified demographic and medical data of the patients.METHODS: A prospective, noninterventional, observational study was conducted in 30 hospitals between May 2014 and July 2016. In total, 2,308 patients with osteoarthritis, 99 patients with rheumatoid arthritis, and 76 patients with ankylosing spondylitis were enrolled. Demographic information (age, sex, body mass index [BMI], alcohol consumption, and smoking) and medical information (type of arthritis, duration of disease, and comorbidities) were collected via a self-administered questionnaire. Patients were observed for more than three months after switching to the combination drug. Data on the QOL (EuroQoL 5-Dimension questionnaire [EQ-5D questionnaire]), medication adherence (Morisky Medication Adherence Scale [MMAS]), and satisfaction were collected at the first and last visits.RESULTS: A total of 2,483 patients enrolled at 30 hospitals completed the questionnaire. After the switch to the combination drug, the mean EQ-5D score improved from 0.72 ± 0.17 to 0.79 ± 0.14 (p < 0.001), and significant improvement was associated with female sex (p = 0.016), shorter disease duration (p < 0.001), and absence of comorbidities (p < 0.001). The mean MMAS score was 6.38 ± 1.77, indicating medium adherence. Satisfaction was significantly higher in female patients (p < 0.001), in patients with a shorter disease duration (p < 0.001), osteoarthritis (p = 0.003), and no comorbidities (p < 0.001). Serious drug-related adverse effects did not occur.CONCLUSIONS: The overall QOL was improved with medium adherence after the switch to the combination drug. On the basis of the analysis of stratified data, sex, age, drinking, smoking, disease duration, comorbidities, and BMI might be associated with QOL, satisfaction, and adherence.

Efectividad Analgésica de Naproxeno Sódico y Etoricoxib Post Extracción Dental Simple: Ensayo Clínico Aleatorizado Paralelo / Analgesic Effectiveness of Sodium Naproxen and Etoricoxib Post Simple Dental Extraction: Parallel Randomized Clinical Trial

RESUMEN: El objetivo de este estudio fue comparar la efectividad analgésica de naproxeno sódico y etoricoxib post extracción dental simple. El presente ensayo clínico, aleatorizado paralelo y ciego simple, se desarrolló en la Clínica Odontológica de la Universidad Privada Antenor Orrego. Los pacientes, quienes requerían exodoncia simple por caries dental en molar mandibular, fueron distribuidos aleatoriamente en tres grupos de 17 participantes cada uno, donde recibieron naproxeno sódico, etoricoxib o ibuprofeno (grupo testigo), según los criterios establecidos. El procedimiento fue estandarizado, evaluándose la eficacia analgésica mediante la escala visual analógica (EVA) a las 1, 8, 24 y 48 horas, después del inicio de la medicación. El análisis estadístico se realizó mediante la prueba de Kruskal-Wallis, considerándose un nivel de significancia del 5 %. No se evidenció diferencia en la efectividad analgésica entre naproxeno sódico y etoricoxib, post extracción dental simple. Este hallazgo se observó a las 1 (p=0,602), 8 (p=0,884), 24 (p=0,338) y 48 horas (p=0,189). No existe diferencia en la efectividad analgésica entre naproxeno sódico y etoricoxib, post extracción dental simple.

ABSTRACT: The aim of the study was to compare the analgesic effectiveness of naproxen sodium and etoricoxib after simple dental extraction. This randomized parallel and single blind clinical trial, was developed in the Clínica Odontológica of the Universidad Privada Antenor Orrego. The patients, who required simple exodontia for dental caries in the mandibular molar, were randomized into three groups of 17 participants each, where they received naproxen sodium, etoricoxib or ibuprofen (control group), according to established criteria. The procedure was standardized, evaluating the analgesic efficacy by means of the analog visual scale at 1, 8, 24 and 48 hours, after the start of the medication. The statistical analysis was carried out using the Kruskal-Wallis test, considering a level of significance of 5 %. There was no difference in the analgesic effectiveness between naproxen sodium and etoricoxib, after simple dental extraction. This finding was observed at 1 (p = 0.602), 8 (p = 0.884), 24 (p = 0.338) and 48 hours (p = 0.189). There is no difference in the analgesic effectiveness between naproxen sodium and etoricoxib, after simple dental extraction.

Riesgo cardiovascular de los antiinflamatorios no esteroideos / Cardiovascular risk of non-steroidal anti-inflammatory drug

Los antiinflamatorios no esteroideos (AINEs) se encuentran entre los fármacos más utilizados en la práctica clínica. Actúan mediante el bloqueo de las enzimas ciclooxigenasas (COX), pero el grado de inhibición de COX-1 y COX-2 varía entre ellos. Se ha generalizado la clasificación entre COX-2 selectivos o coxibs, y los no selectivos o AINEs tradicionales. Tanto los efectos analgésico y antiinflamatorio como los efectos adversos cardiovasculares dependen de la inhibición de COX-2. Este trabajo revisa las evidencias disponibles del aumento del riesgo de eventos trombóticos tanto para los coxibs como para los AINEs tradicionales. El efecto protrombótico podría deberse a la inhibición de la COX-2 endotelial, con disminución de la prostaciclina y un incremento relativo de los niveles del tromboxano plaquetario. Los coxibs y el diclofenac, 150 mg/día, aumentarían el riesgo de eventos vasculares mayores en más de un tercio. El ibuprofeno 2400 mg/día aumentaría levemente el riesgo de eventos coronarios. El naproxeno 1000 mg/día no incrementaría el riesgo de eventos vasculares. Además, el ibuprofeno y el naproxeno tienen el potencial del disminuir el efecto cardioprotector de bajas dosis de aspirina. El naproxeno (≤ 1000 mg/día) y el ibuprofeno a bajas dosis (≤ 1200 mg/día) deberían considerarse los AINEs con el mejor perfil de seguridad cardiovascular. Las decisiones terapéuticas deben basarse en una adecuada evaluación del riesgo del paciente, utilizando los AINEs más seguros, a las menores dosis efectivas, por el menor tiempo posible que permita el control de los síntomas, restringiendo su utilización en enfermos con aumento del riesgo cardiovascular.

Non-steroidal anti-inflammatories (NSAIDs) are among the most commonly used drugs in clinical practice. They block cyclooxygenases (COX) enzymes, but the degree of inhibition of COX-1 and COX-2 varies between them. In general, NSAIDs are classified in selective COX-2 or coxibs and non-selective or traditional NSAIDs. Both the analgesic and anti-inflammatory effects, as well as the cardiovascular adverse effects, depend on the COX-2 inhibition. This paper reviews the available evidence of the increased risk of thrombotic events for both coxibs and traditional NSAID. The prothrombotic effect could be due to the inhibition of endothelial COX-2, with a decrease in production of prostacyclin and a relative increase in platelet thromboxane levels. Coxibs and diclofenac 150 mg/day seem to increase the risk of major vascular events by more than a third. Ibuprofen 2400 mg/day could slightly increase the risk of coronary events. Naproxen 1000 mg/day apparently does not increase the risk of vascular events. Besides ibuprofen and naproxen have the potential to decrease the cardioprotective effect of low doses of aspirin. Naproxen (≤ 1000 mg/day) and low doses of ibuprofen (≤ 1200 mg/day) are considered to have the most favorable thrombotic cardiovascular safety profiles of all NSAIDs. Therapeutic decisions should be based on an assessment of a person´s individual risk factors, using the safest NSAIDs, at the lowest effective doses, for the shortest duration necessary to control symptoms, restricting their use in patients with increased cardiovascular risk.

Evaluation of naproxen-induced oxidative stress, hepatotoxicity and in-vivo genotoxicity in male Wistar rats / 药物分析学报

Naproxen (NP), a nonsteroidal anti-inflammatory drug (NSAID), is used for the treatment of common pain, inflammation and tissue damage. Genotoxicity testing of NP is of prime importance as it represents the largest group of drugs to which humans are exposed. Not many genotoxic studies are reported on NP; therefore, the present study investigated the detailed genotoxic and oxidative stress properties of NP. Male Wistar rats were administered NP orally at the doses of 38.91 and 65.78 mg/kg body weight for 14 days. Reduced glutathione (GSH), superoxide dismutase (SOD), catalase (CAT) and lipid peroxidation (LPO) activities/levels were measured in the liver, kidney and brain tissues. The aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP) activities, and total bilirubin (TBIL) levels were measured in the liver tissues. Micronucleus frequency (micronucleus test MNT) and DNA damage (comet assay) were performed in the bone marrow cells and leukocytes, respectively. The results showed that NP treatment decreased the GSH levels and increased the SOD, CAT, LPO, ALT, AST, ALP and TBIL activities/levels compared to the control (p < 0.05). Results of MNT showed an increased micronucleus induction and comet assay showed a significant increase in DNA damage in the NP treated animals (p < 0.05). Treatment of NP resulted in the biochemical imbalance and induced oxidative stress that deteriorated the integrity of the cells, which caused significant damage to the genetic material and affected liver function in male Wistar rats. Therefore, NP is a potential genotoxic agent that induces genotoxicity and oxidative stress.

Effect of a 5% naproxen patch on reducing pain caused by separators prior to fixed orthodontic treatment

BACKGROUND: The pain involved in orthodontic treatments may involve inflammatory processes. This study evaluated the effect of using a naproxen patch for pain reduction in the separating stage of fixed orthodontic treatment. METHODS: In this double-blind, randomized, controlled clinical trial of 35 orthodontic patients (age: 14–19 years) who had pain during separator placement, each patient randomly placed naproxen and placebo patches in the first permanent molar region, in opposite quadrants of the same jaw. Patches were replaced every 8 hours until 3 days after separator placement. Patients recorded their pain perception at 2, 6, and 24 hours, and on days 2 (6 PM), 3 (10 AM and 6 PM), and 7 (10 AM and 6 PM), using a visual analog scale. Mean pain scores were compared for the two patches, and effects of sex and age thereon determined. RESULTS: Data from 29 patients (21 girls, eight boys) were analyzed. Mean pain values decreased over time for both patches (P < 0.001). Recorded pain did not differ significantly between the sexes (P = 0.059) or between those aged <16 and those ≥16 years (P = 0.106). Mean pain recorded with naproxen patches was statistically significantly less than that with placebo patches at all time points (P = 0.004). CONCLUSION: The naproxen patch was more efficient than the placebo patch for reducing pain at all time points. The highest pain score was recorded at 6 hours, and the least pain was recorded at the 7th day after separator placement.

Comparison of the postoperative analgesic effects of naproxen sodium and naproxen sodium-codeine phosphate for arthroscopic meniscus surgery / Comparação dos efeitos analgésicos pós-operatórios de naproxeno sódico e naproxeno sódico-fosfato de codeína em artroscopia de menisco

ABSTRACT BACKGROUND AND OBJECTIVES: Nonsteroidal anti-inflammatory drugs (NSAIDs) are frequently used to control arthroscopic pain. Addition of oral effective opioid "codeine" to NSAIDs may be more effective and decrease parenteral opioid consumption in the postoperative period. The aim of this study was to compare the efficacy and side effects of naproxen sodium and a new preparation naproxen sodium-codeine phosphate when administered preemptively for arthroscopic meniscectomy. METHODS: Sixty-one patients were randomized into two groups to receive either oral naproxen sodium (Group N) or naproxen sodium-codeine phosphate (Group NC) before surgery. The surgery was carried out under general anesthesia. Intravenous meperidine was initiated by patient-controlled analgesia (PCA) for all patients. The primary outcome measure was pain score at the first postoperative hour assessed by the Visual Analogue Scale (VAS). Sedation assessed by Ramsey Sedation Scale, first demand time of PCA, postoperative meperidine consumption, side effects and hemodynamic data were also recorded. RESULTS: The groups were demographically comparable. Median VAS scores both at rest and on movement were significantly lower in Group NC compared with Group N, except 18th hour on movement (p < 0.05). The median time to the first demand of PCA was shorter in Group N compared with Group NC (p < 0.001). Meperidine consumption was higher in Group N compared with Group NC (p < 0.001). There was no difference between groups with respect to side effects (p > 0.05). CONCLUSIONS: The combination of naproxen sodium-codeine phosphate provided more effective analgesia than naproxen sodium and did not increase side effects.

RESUMO JUSTIFICATIVA E OBJETIVOS: Os anti-inflamatórios não esteroides (AINEs) são frequentemente usados para controlar a dor após artroscopia. A adição de um opiáceo oral eficaz (codeína) aos AINEs pode ser mais efetiva e diminuir o consumo de opiáceo parenteral no pós-operatório. O objetivo deste estudo foi comparar a eficácia e os efeitos colaterais de naproxeno sódico e uma nova preparação, naproxeno sódico-fosfato de codeína, quando administrados preventivamente para meniscectomia artroscópica. MÉTODOS: Foram randomicamente divididos em dois grupos 61 pacientes para receber naproxeno sódico por via oral (Grupo N) ou naproxeno sódico-fosfato de codeína (Grupo NC) antes da cirurgia. A cirurgia foi feita sob anestesia geral. Meperidina intravenosa foi iniciada por meio de analgesia controlada pelo paciente (ACP) para todos os pacientes. O desfecho primário foi o escore de dor na primeira hora de pós-operatório, avaliada com a escala visual snalógica (EVA). A sedação foi avaliada com a escala de sedação de Ramsey. A primeira demanda de ACP, o consumo de meperidina no pós-operatório, os efeitos colaterais e os dados hemodinâmicos também foram registrados. RESULTADOS: Os grupos foram demograficamente comparáveis. As medianas dos escores EVA tanto em repouso quanto em movimento foram significativamente menores no Grupo NC comparado com o Grupo N; exceto para movimento na avaliação de 18 horas (p < 0,05). A mediana do tempo até a primeira demanda de ACP foi menor no Grupo N em comparação com o Grupo NC (p < 0,001). O consumo de meperidina foi maior no Grupo N em comparação com o Grupo NC (p < 0,001). Não houve diferença entre os grupos em relação aos efeitos colaterais (p > 0,05). CONCLUSÕES: A combinação de naproxeno sódico-fosfato de codeína forneceu analgesia mais efetiva que naproxeno sódico, sem aumentar os efeitos colaterais.

Synthesis of twin drugs of paeonol and study on their degradation dynamics properties and anti-inflammatory activities / 中国药学杂志

OBJECTIVE: To synthesize the ester condensation products of paeonol by coupling paeonol or its analogues with naproxen and investigate the anti-inflammatory activities of the products. METHODS: Five compounds were synthesized by condensing paeonol or its analogues with naproxen by DCC method. An HPLC method was established for determination of the content of the target products, and their degradation dynamics under pH 1.2, 5.0 and 7.4 buffer conditions at 37℃ was studied. The anti-inflammatory activities of the compounds were evaluated in xylene-induced mouse ear swelling model. RESULTS: Five new compounds were synthesized and confirmed by MS and H-NMR. Degradation kinetic experiments showed that these compounds were stable in buffers of different pHs. All the compounds showed anti-inflammatory activities. CONCLUSION: All the compounds are stable and exhibit potent anti-inflammatory activities.

Efeito protetor do Nitrosil-Rutênio (Cis[Ru(bpy)2SO3NO]+(PF6) em modelos experimentaisde lesões gástricas em camundongos – envolvimento da via NO/GCS/KATP

Lesões gástricas relacionadas ao consumo excessivo de antiinflamatórios não esteroidais (AINEs) e etanol possuem um importante papel na gastroenterologia clínica. Fármacos com ação anti-secretória gástrica, como os inibidores da bomba de prótons, representam a principal opção na terapia destas patologias. Objetivo: Avaliar o efeito do doador de NO nitrosil-rutênio (Rut-NO) na defesa da mucosa gástrica em modelos experimentais de lesão gástrica em camundongos e a participação da guanilato ciclase solúvel (GCs) e dos canais de KATP neste efeito. Métodos: Protocolo1-Camundongos swiss foram pré-tratados com Rut-NO (3mg/Kg, v.o), rutênio (2.3mg/Kg, v.o) ou nitroprussiato (NPS) na dose de 10mg/kg, v.o, meia hora antes da administração por gavagem de etanol 50%. Em outro grupo, os animais foram pré-tratados com ODQ (10mg/Kg, v.o) ou glibenclamida (10mg/Kg,i.p) trinta minutos ou 1h antes, respectivamente dos tratamentos citados anteriormente.Depois de 1h, os animais foram sacrificados e os estômagos removidos para a avaliação das lesões gástricas por planimetria computadorizada. Além disso, fragmentos de tecido foram removidos para análise microscópica e dosagem de glutationa (GSH) e malondialdeído (MDA)...

Gastric lesions associated to excessive consumption of nonsteroidal anti-inflammatory drugs (NSAIDs) and ethanol have an important role in clinical gastroenterology. The drugs with gastric antisecretory action, suchas proton pump inhibitors, represent the main option in the treatment of these pathologies. Aim: To evaluate the effect of NO donor nitrosyl-ruthenium (Rut-NO) in gastric mucosal defense in experimental models of gastric damage in mice, as wellthe involvement of soluble guanylate cyclase (sGC) and KATPchannels in this effect. Methods: Protocol 1-mice were pre-treated with Rut-NO (3mg/Kg, vo), ruthenium (2.3mg/Kg, p.o) or nitroprusside (SNP) at a dose of 10mg/kg, p.o, half an hour before administration by gavage of 50% ethanol. In another group, the animals were pre-treated with ODQ (10mg/kg, po) or glibenclamide (10mg/kg, ip) thirty minutes or 1 hour prior, respectively,the treatments mentioned above. After 1h, the animals were sacrificed and the stomachsremoved for evaluation of gastric lesions by computerized planimetry. In addition, fragments of tissue were removed for microscopic analysis and measurement of glutathione (GSH) and malondialdehyde (MDA) levels...

Analgesic effectiveness of prophylactic therapy and continued therapy with naproxen sodium post simple extraction / Efectividad analgésica post exodoncia simple de la terapia profiláctica y la terapia continuada con naproxeno sódico

To compare the analgesic effectiveness of the prophylactic therapy and continued therapy with naproxen sodium after a simple dental extraction. Material and methods: This prospective randomized, parallel, single blind clinical trial was developed in the Dental Clinic of the Universidad Alas Peruanas in Trujillo (Peru). The patients, who required simple extraction due to dental caries, were randomly distributed into three groups: 30 of them took 550mg naproxen sodium in the preoperative period and then every 12 hours, other 30 took 550mg naproxen sodium in the postoperative period and then every 12 hours, and 30(control group), received 400mg ibuprofen in the postoperative period and then every 8 hours, depending on the established criteria. The procedure was standardized, analgesic effectiveness was assessed by visual analog scale and the presence of adverse drug reactions was evaluated as well. Data were analyzed using ANOVA and Duncan’s test using IBM SPSS 22 with a significance level of 5 percent. Results: Continued therapy with naproxen sodium showed greater analgesic effectiveness after a simple extraction at 1, 8 and 24 hours (p<0.005). Conclusion: Continued therapy with naproxen sodium presented greater effectiveness than prophylactic therapy with naproxen sodium after a simple extraction...

Comparar la efectividad analgésica post exodoncia simple entre la terapia profiláctica y la terapia continuada con naproxeno sódico. Material y métodos: Ensayo clínico, prospectivo aleatorizado, paralelo y simple ciego, se desarrolló en la Clínica Estomatológica de la Universidad Alas Peruanas Filial Trujillo (Perú). Los pacientes, quienes requerían exodoncia simple por caries dental, fueron distribuidos aleatoriamente en tres grupos: 30 recibieron naproxeno sódico 550 mg en el preoperatorio y luego cada 12 horas, 30 recibieron naproxeno sódico de 550 mg en el postoperatorio y luego cada 12 horas y, 30, ibuprofeno (grupo testigo) de 400 mg en el posoperatorio y luego cada 8 horas, según los criterios establecidos. El procedimiento fue estandarizado, evaluándose la eficacia analgésica, mediante la escala visual analógica, y la presencia de reacciones adversas medicamentosas. Los datos fueron analizados mediante el ANOVA y el test de Duncan empleando IBM SPSS Statistics 22. Resultado: La terapia continuada con naproxeno sódico presentó mayor efectividad analgésica post exodoncia simple a las 1, 8 y 24 horas (p<0,005). Conclusión: la terapia continuada con naproxeno sódicopresentó mayor efectividad que la terapia profiláctica con naproxeno sódico post exodoncia simple...

Chiral Separation of Naproxen Enantiomers by Supercritical Fluid Chromatography / 中国药房

OBJECTIVE:To develop a method for the separation of naproxen enantiomers. METHODS:The supercritical fluid chromatography(SFC)method was adopted. The chiral column,type and proportion of polar additive in mobile phase,back pres-sure and column temperature were optimized using the separation time,capacity factor,separation factor and separation degree as index. RESULTS:The best condition was on the chiral column CHIRALPAK?AD-H,with polar additive of isopropanol (20%), back pressure of 170 bar,column temperature of 20℃and the detection wavelength of 283 nm. Under this condition,baseline sep-aration of naproxen enantiomers can be achieved;separation degree was 4.31 and separation factor was 1.90;RSD of precision,sta-bility and reproducibility tests were no more than 2.65%(n=5). CONCLUSIONS:Established method is simple,reproducible and well-separated,and can be used for chiral separation of naproxen enantiomers.

A New Bioanalytical Method Development & Validation for Simultaneous Estimation of Esomeprazole and Naproxen in Human Plasma by Using RP-HPLC.

Aim: A new reverse phase high performance liquid chromatography (RP-HPLC) method for the quantitative determination of Esomeprazole and Naproxen in human plasma was developed and validated as per US-FDA guidelines. Methodology: The drug was spiked in the plasma and extracted with mobile phase by precipitation method. The extracted analyte was injected into Symmetry C18 (4.6 x 150mm, 5μm, Make: XTerra) or equivalent, maintained at ambient temperature and effluent was monitored at 285nm. The mobile phase was composed of potassium dihydrogen phosphate and acetonitrile [HPLC Grade] in the ratio of 60:40. The pH of the potassium buffer was adjusted to 3.0 by using Ortho Phosphoric Acid. The flow rate was maintained at 1.0 mL/min. Results: The developed method shows high specificity for Esomeprazole and Naproxen. The calibration curve for Esomeprazole and Naproxen was linear from 1.0 to 6.0 ppm (r2= 0.999) and 25.0 to 150.0 ppm (r2= 0.999) respectively. The inter-day and intra-day precision was found to be within limits. The proposed method was adequate sensitivity, reproducibility, and specificity for the determination of esomeprazole and naproxen in plasma. The Lower limit of quantification (LLOQ) for the drug Esomeprazole and Naproxen were found to be 0.04μg/ml and 0.4μg/ml respectively. The average percent recovery for the drugs Esomeprazole and Naproxen were found to be 98.97-99.84 & 99.80-100.95 respectively and reproducibility was found to be satisfactory. Conclusion: The proposed method was accurate, and precise for the quantification of Esomeprazole and Naproxen in the plasma. The proposed can also be used for routine analysis in quality control. The method was validated for parameters like selectivity, sensitivity, precision, intermediate precision, accuracy, linearity, recovery & stability. This RP -HPLC method is suitable for determining the concentration of Esomeprazole and Naproxen in plasma and it can applied for routine analysis for determination of the Esomeprazole and Naproxen from dosage form during pharmacokinetic study.

Estabilidad de supositorios de naproxeno para uso infantil y adulto / Stability of Naproxen suppositories for children and adults

INTRODUCCIÓN: el naproxeno en supositorios para uso infantil y adulto constituye una de las líneas de investigación en desarrollo de la Empresa Roberto Escudero Díaz. Los estudios de estabilidad son una parte indispensable para el registro de una nueva formulación. OBJETIVO: determinar la estabilidad de los supositorios de naproxeno para uso infantil y adulto, teniendo en cuenta la estabilidad física y química del analito en las nuevas formulaciones. MÉTODOS: se realizó el estudio de estabilidad para formulaciones en fase de desarrollo de supositorios de naproxeno para uso infantil y adulto, teniendo en cuenta la metodología propuesta por el Centro para el Control Estatal de la Calidad de los Medicamentos (CECMED). Se emplearon para cada dosis evaluada, supositorios de tres lotes pilotos envasados en tiras de aluminio termosellables. Se almacenaron los supositorios a temperatura de refrigeración (2-8 °C) y ambiente (30 ± 2 °C) durante un año, y se les realizaron muestreos a los 0, 1, 3, 6 y 12 meses de elaborados. Para el análisis de la estabilidad química, se consideraron los resultados del contenido de naproxeno obtenidos por volumetría de neutralización y por cromatografía líquida de alta resolución, así como la determinación de los posibles productos de degradación por cromatografía en capa delgada. RESULTADOS: se demostró la adecuada estabilidad física de los supositorios de ambas dosis, independientemente de la temperatura de almacenamiento durante 12 meses, ya que se mantuvieron inalteradas las características organolépticas y el peso. Aunque el tiempo de liquefacción disminuyó durante el almacenamiento, siempre fue inferior al límite establecido. Con el método por cromatografía líquida de alta resolución, se detectaron pequeños cambios en la concentración de analito, por lo que este método fue superior para el seguimiento de la estabilidad química que la volumetría de neutralización. No se detectaron productos de degradación en los supositorios por ninguna de las técnicas cromatográficas utilizadas. CONCLUSIONES: los supositorios fueron estables desde el punto de vista físico y químico a temperatura de refrigeración (2-8 °C) y ambiente (30 ± 2 °C) durante 12 meses(AU)

INTRODUCTION: Naproxen suppository for children and adults is one of the developing research lines of Roberto Escudero Diaz drug production enterprise. The stability studies are indispensable for the registration of a new formulation. OBJECTIVE: to determine the stability of Naproxen suppositories for children and adults, taking the physical and chemical stability of the analyte into account in the new formulations. METHODS: pursuant to the methodology of the Center for the State Quality Control of Drugs (CECMED), the stability study for developing formulations was conducted in Naproxen suppositories for children and adults. These products packaged in heat-seal aluminum blister packs from three pilot batches were used for each evaluated dose. They were stored at 2 to 8 °C refrigeration and at air temperature of 30 ± 2 °C during one year, and sampled at 0, 1, 3, 6 and 12 months after preparation. For the analysis of the chemical stability, the Naproxen content determined by the neutralizing volumetry and high performance liquid chromatography tests and the possible degradation products identified in the thin layer chromatography test were taken into account. RESULTS: this study proved the adequate physical stability of suppositories at both doses regardless of the storage temperatures during 12 months because their organoleptic characteristics and weight remained unchanged. Although the liquefaction time decreased under the storage conditions, it was lower than the set limit. The high performance liquid chromatography detected slight changes in the analyte concentration, so this method was better for the chemical stability analysis than the neutralization volumetry method. The chromatographic techniques did not detect any degradation product in the suppositories. CONCLUSIONS: the suppositories were physically and chemically stable at a refrigerating temperature of 2 to 8 °C and at air temperature of 30 ± 2 °C during 12 months(AU)

Effects of nanosuspension and inclusion complex techniques on the in vitro protease inhibitory activity of naproxen

This study investigated the effects of nanosuspension and inclusion complex techniques on in vitro trypsin inhibitory activity of naproxen—a member of the propionic acid derivatives, which are a group of antipyretic, analgesic, and non-steroidal anti-inflammatory drugs. Nanosuspension and inclusion complex techniques were used to increase the solubility and anti-inflammatory efficacy of naproxen. The evaporative precipitation into aqueous solution (EPAS) technique and the kneading methods were used to prepare the nanosuspension and inclusion complex of naproxen, respectively. We also used an in vitro protease inhibitory assay to investigate the anti-inflammatory effect of modified naproxen formulations. Physiochemical properties of modified naproxen formulations were analyzed using UV, IR spectra, and solubility studies. Beta-cyclodextrin inclusion complex of naproxen was found to have a lower percentage of antitryptic activity than a pure nanosuspension of naproxen did. In conclusion, nanosuspension of naproxen has a greater anti-inflammatory effect than the other two tested formulations. This is because the nanosuspension formulation reduces the particle size of naproxen. Based on these results, the antitryptic activity of naproxen nanosuspension was noteworthy; therefore, this formulation can be used for the management of inflammatory disorders.

O objetivo do presente estudo foi investigar a atividade anti-inflamatória in vitro de nanossuspensões e do complexo de inclusão contendo naproxeno. Esse fármaco é derivado de ácido propiônico, com ação analgésica, antipirética e antiinflamatória. A obtenção dessas formulações teve por finalidade o aumento da solubilidade e da atividade anti-inflamatória do fármaco. Os métodos por precipitação em solução aquosa por evaporação e por empastagem foram modificados para a obtenção da nanossuspensão e do complexo de inclusão, respectivamente. Para a avaliação da atividade anti-inflamatória das formulações utilizou-se ensaio in vitro modificado de inibição de tripsina. As propriedades físico-químicas das formulações propostas foram determinadas utilizando espectroscopia UV e de infravermelho, além de estudos de solubilidade. O complexo de inclusão de naproxeno apresentou menor atividade antitripsina, quando comparado ao composto livre e à nanossuspensão. Em conclusão, entre as formulações avaliadas, a nanossuspensão de naproxeno apresentou maior efeito anti-inflamatório. Esse efeito foi devido à redução da dimensão das partículas de naproxeno para a escala nanométrica. Com base nos resultados obtidos, a atividade da nanossuspensão de naproxeno foi notável. Dessa forma, essa formulação apresenta potencial para o tratamento de distúrbios inflamatórios.

Formulation development of directly compressed Naproxen SR tablet using Kollidon SR and Avicel PH 102 polymer.

Naproxen is a well-known non-steroidal anti-inflammatory drug (NSAID). This work has been done for developing a formulation of 280 mg sustained release (SR) tablet where 150 mg active pharmaceutical ingredient (Naproxen) were used along with other excipients like Kollidon SR, Avicel PH 102, Lactose MH, Povidone K 30 and Mg-Stearate. Naproxen SR tablet was prepared by direct compression method aiming to enhance its dissolution properties. The physical parameters (hardness, thickness, diameter, average weight and friability) and drug release profile of this tablet were evaluated. The hardness of tablets from F1 and F2 formulation were highest and rest of them was also satisfactory. F2 formulation did not meet the friability test. But rests of the formulations were acceptable which indicate that others formulations can handle pressure during storage, transportation and packaging. All the formulations released 90% of drug within 120 minutes except F4 formulation. Among the six formulations, release was prompt in F1 formulation because of usage of higher concentration of polymer Kollidon SR. The outcome of this study indicates that the rate of dissolution of Naproxen SR tablet can be considerably improved with Kollidon SR.

Simultaneous spectrophotometric estimation of esomeprazole and naproxen in bulk and tablet dosage form.

Esomeprzole and naproxen are available in tablet dosage form in the ratio 1:25. Two simple, accurate, precise and economic methods; simultaneous equation method and multicomponent method have been described for the simultaneous estimation of esomeprzole and naproxen in tablet dosage form. Absorption maxima of esomeprzole and naproxen in distilled water were found to be 301.0 nm and 262.0 nm respectively. Beer’s law was obeyed in the concentration range 5-50 μg/ml for esomeprzole and 5-50 μg/ml for naproxen. The methods allow rapid analysis of binary pharmaceutical formulation with accuracy. Results of two methods were validated statistically and by recovery studies and were found to be satisfactory.

Formulation development of directly compressed Naproxen SR tablet using Kollidon SR and Avicel PH 102 polymer.

Naproxen is a well-known non-steroidal anti-inflammatory drug (NSAID). This work has been done for developing a formulation of 280 mg sustained release (SR) tablet where 150 mg active pharmaceutical ingredient (Naproxen) were used along with other excipients like Kollidon SR, Avicel PH 102, Lactose MH, Povidone K 30 and Mg-Stearate. Naproxen SR tablet was prepared by direct compression method aiming to enhance its dissolution properties. The physical parameters (hardness, thickness, diameter, average weight and friability) and drug release profile of this tablet were evaluated. The hardness of tablets from F1 and F2 formulation were highest and rest of them was also satisfactory. F2 formulation did not meet the friability test. But rests of the formulations were acceptable which indicate that others formulations can handle pressure during storage, transportation and packaging. All the formulations released 90% of drug within 120 minutes except F4 formulation. Among the six formulations, release was prompt in F1 formulation because of usage of higher concentration of polymer Kollidon SR. The outcome of this study indicates that the rate of dissolution of Naproxen SR tablet can be considerably improved with Kollidon SR.

Improved dissolution and micromeritic properties of naproxen from spherical agglomerates: preparation, in vitro and in vivo characterization

Naproxen, an anti-inflammatory drug, exhibits poor aqueous solubility, which limits the pharmacological effects. The present work was carried out to study the effect of agglomeration on micromeritic properties and dissolution. Naproxen agglomerates were prepared by using a three solvents system composed of acetone (good solvent), water (non-solvent) and dichloromethane (bridging liquid). Differential Scanning Calorimetry (DSC) results showed no change in the drug after crystallization process. X-Ray Powder Diffraction (XRPD) studies showed the sharp peaks are present in the diffractograms of spherical agglomerates with minor reduction in height of the peaks. The residual solvents are largely below the tolerated limits in the agglomerates. Scanning Electronic Microscopy (SEM) studies showed that agglomerates were spherical in structure and formed by cluster of small crystals. The agglomerates exhibited improved solubility, dissolution rate and micromeritic properties compared to pure drug. Anti-inflammatory studies were conducted in Wistar strain male albino rats and naproxen agglomerates showed more significant activity than the pure drug.

Naproxeno, fármaco anti-inflamatório, apresenta baixa solubilidade em água, o que limita os efeitos farmacológicos. O presente trabalho foi realizado para estudar o efeito da aglomeração nas propriedades micromeríticas e na dissolução. Aglomerados de naproxeno foram preparados por meio da utilização de sistema de três solventes composto de acetona (bom solvente), água (não-solvente) e diclorometano (líquido de ligação). A DSC não resulta mostrou nenhuma mudança na droga depois de processo de cristalização. Estudos de difração de Raios X do Pó (XRPD) mostraram picos agudos nos difratogramas de aglomerados esféricos, com redução mínima dea altura dos picos. Os solventes residuais estão amplamente abaixo dos limites tolerados nos aglomerados. Os estudos de Microscopia Eletrônica de Varredura (SEM) mostraram que esses aglomerados eram de estrutura esférica e formados por grupos de pequenos cristais. Os aglomerados apresentaram solubilidade, taxa de dissolução e propriedades micromeríticas aprimoradas em comparação com o fármaco puro. Estudos anti-inflamatórios foram conduzidos em ratos Wistar albinos masculinos e os aglomerados de naproxeno mostraram atividade mais significativa do que o fármaco puro.