Novel RP-HPLC method for estimation of a newly developed combination of tizanidine and etoricoxib in rat plasma: Eight criteria for greens evaluation.

A novel environmentally friendly reversed-phase high-performance liquid chromatography (RP-HPLC) method has been effectively validated for simultaneously measuring a prospective conjunction of tizanidine (TIZ) and etoricoxib (ETC), the combined medicine, in rat plasma. The technique employs diclofenac potassium as the internal standard, guaranteeing dependable and precise outcomes. This study aimed to assess the impact of the suggested combination therapy on treating inflammation resulting from rheumatoid arthritis (RA) in a rat model. The procedure was performed using an Agilent series 1200 model HPLC apparatus. The chromatographic conditions consist of isocratic elution mode, C18 column with dimensions of 150 mm × 4.6 mm × 5 µm, flow rate of 1.5 mL/min, wavelength of 230 nm, temperature of 50°C, and injection volume of 10 µL. The elution was performed using a mobile phase consisting of a phosphate buffer with a pH of 3.5 and acetonitrile in a ratio of 80:20 v/v. Calibration curves were conducted for TIZ and ETC within the 1-50 µg/mL range, demonstrating linear trends with R2 values over 0.999. The effectiveness and eco-friendliness of the proposed method were evaluated using eight separate environmentally conscious metrics. The addition of TIZ and ETC to arthritic rodents amplified these effects significantly. Furthermore, TIZ and ETC significantly reduced serum levels in arthritic rodents, and safety investigations revealed normal complete blood count, liver, and renal functions. TIZ and ETC appear to have antiarthritic, anti-inflammatory, and safe combinations, making them viable future treatment options for RA that are also safe and efficacious. Following validation by United States Food and Drug Administration (US-FDA) rules, all goods met the criteria.

Comparing pre- and postoperative etoricoxib administration versus only postoperative on third molar extraction sequelae and oral health quality of life: a prospective quasi-experimental study.

OBJECTIVES: This study aimed to compare the impact of pre- and postoperative etoricoxib administration versus only postoperative on third molar extraction sequelae and oral health quality of life. MATERIALS AND METHODS: This prospective quasi experimental study involved 56 patients, divided into a study group receiving preemptive etoricoxib 120 mg before surgery and postoperative etoricoxib 120 mg (n = 28), and a control group receiving preemptive placebo before surgery and postoperative etoricoxib 120 mg (n = 28). Follow-up assessments were conducted at 3- and 7-days post-surgery, recording swelling, trismus, and adverse events. Patients rated perceived pain using the visual analog scale (VAS) and completed an oral health-related quality of life (OHRQoL) questionnaire at specified intervals. Statistical analysis employed non-parametric tests (i.e., the Mann-Whitney test, Friedman test, and Wilcoxon sign test) with P < 0.05. RESULTS: Significantly lower VAS scores were reported in the study group throughout the follow-up period (P < 0.05). Pharmacological protocol did not have a significant impact on postoperative edema and trismus (P > 0.05). However, double etoricoxib intake significantly improved postoperative quality of life on day 3 after surgery (P < 0.05). CONCLUSIONS: Pre- and postoperative etoricoxib 120 mg intake in third molar surgery reduced postoperative pain and enhanced postoperative quality of life on day 3 after surgery. Importantly, it was equally effective in managing swelling and trismus compared to exclusive postoperative intake. CLINICAL RELEVANCE: Preemptive etoricoxib use may decrease patient discomfort following impacted mandibular third molar extraction.

Fabrication of gastro-floating sustained-release etoricoxib and famotidine tablets: design, optimization, in-vitro, and in-vivo evaluation.

In this study, a new gastro-floating sustained-release tablet (GFT) with a combination of Etoricoxib (ET) and Famotidine (FM) was successfully developed. GFTs were prepared by using a combination of hydrophilic swellable natural/semi-synthetic polymers as a controlled-release layer. Through a 24 full factorial statistical experimental design, the effects of formulation factors on the release of GFTs were conducted. The ideal floating tablet (FT) comprised konjac-gum (150 mg), guar-gum (26.57 mg), xanthan-gum (54.17 mg), and HPMC-K15-M (69.25 mg). The ideal FT exhibited a high swelling index (SI) (297.7%) and rapid FLT (around 50 s) in 0.1 N HCl as well as controlled release of ET (22.43% in 1 h and 77.47% in 8 h) and FM (24.89% in 1 h and 93.82% in 8 h) with the absence of any drug-excipient interactions. The AUC0∼72 (ng h/mL) of ET and FM in the GFTs were approximately double-fold of the market, respectively. The relative bioavailability was (207.48 ± 12.02% and 208.51 ± 13.11%) compared with commercial tablets. The X-ray imaging showed a promising buoyancy ability for approximately 8 h. These findings revealed the successful preparation of the sustained-release floating tablet with improved dual drug delivery.

Quality by design-based development and in vitro evaluation of dual release tablet of etoricoxib and thiocolchicoside: A novel chronotherapeutic approach for arthritis pain management.

OBJECTIVE: The traditional drug delivery system is not much effective when treating chronopathological diseases like arthritis. Consequently, there is a gap in the market for a delivery system that can provide an explicit treatment following the chronopharmacology of this disorder. The present study is based on the objective to develop Eudragit coated dual release bilayer tablet designed by the quality by design (QbD) and based on the chronotherapeutic approach. The dual release tablet contained an immediate release layer of etoricoxib and a sustained release layer of thiocolchicoside. MATERIAL AND METHOD: The quality target product profile (QTTP) of the formulation was established along with critical quality attributes (CQA). The optimization of the dual release layer was done using a three-level, three-factor Box-Behnken design. A total of thirteen formulations of etoricoxib (ET1-ET13) and thiocolchicoside (TH1-TH13) were developed based on the design composition of etoricoxib, sodium starch glycolate and sodium bicarbonate for the immediate release (IR) layer and thiocolchicoside, HPMC E5 LV and magnesium stearate for the sustained release (SR) layer respectively. The developed dual release layers were compressed to form a bilayer tablet. The bilayer tablets were further coated with pH-dependent polymer Eudragit S-100 to avoid drug release in upper GIT. The initial characterization and drug-excipient interaction studies were performed initially using infra-red (IR) spectroscopy and X-ray diffraction studies (XRD). Formulations showing good micrometric properties, disintegration and drug release were selected for final compression of bilayer tablets. RESULT: Formulation ET13 showed the fastest drug release (88%) at 15minutes and quick disintegration time (21s). The sustained release thiocolchicoside tablet layer (TH1-TH13) had a hardness that varied from 4.01 to 4.45kg/cm2. Formulation TH12 had the highest hardness, whereas TH6 showed the lowest hardness. The sustained release layer showing 97.63% of drug release after 8hours was selected for the compression to bilayer tablet. The developed dual layer tablets were investigated for quality parameters like hardness, percentage friability, weight variation, disintegration and dissolution. CONCLUSION: A high level of patient compliance is ensured through the current design as the patient does not need to get out of bed at night to take the medication.

Selective COX-2 Inhibitor Etoricoxib's Liposomal Formulation Attenuates M2 Polarization of TAMs and Enhances its Anti-metastatic Potential.

INTRODUCTION: COX-2 inhibition in pro-tumoral M2 polarization of Tumor-Associated Macrophages (TAMs) underscore the improved prognosis and response to cancer therapy. Thus, etoricoxib, a COX-2 inhibiting NSAID drug is highly effective against tumorigenesis, but its compromised solubility and associated hepatotoxicity, and cardiotoxicity limit its clinical translation. OBJECTIVE: In view of the consequences, the proposed study entails the development of a liposomal formulation for etoricoxib and evaluates its anticancer potential. METHODS AND RESULT: Etoricoxib loaded liposome was prepared by thin layer hydration method and characterized as a nearly monodisperse system with particle size (91.64 nm), zeta potential (-44.5 mV), drug loading (17.22%), and entrapment efficiency (94.76%). The developed formulation was administered subcutaneously into the orthotopic 4T1/Balb/c mice model. Its treatment significantly reduced tumor size and skewed M2 polarization of TAMs to a greater extent against free etoricoxib. Furthermore, Tumor tissues analyzed through immunoblotting study confirmed the reduction in Akt phosphorylation at Thr308 residue and pro-tumoral VEGF, MMP-9, and MMP-2 proteins; Moreover, histology studies and microCT analysis of bones revealed the enhanced anti-metastatic potential of etoricoxib delivered through developed formulation against free etoricoxib. CONCLUSION: As an epilogue, the developed formulation efficiently delivers poorly soluble etoricoxib, enhances its therapeutic potential as an anti-tumor and anti-metastatic agent, and directs explorative research for clinical translation.

Comparison of preemptive etoricoxib and dexamethasone in third molar surgery - a randomized controlled clinical trial of patient-reported and clinical outcomes.

OBJECTIVES: To compare preemptive single-dose etoricoxib and dexamethasone on postoperative patient satisfaction (pPS) and clinical parameters following the impacted mandibular third molar (IMTM) extraction. MATERIALS AND METHODS: A parallel-group, triple-blinded, controlled clinical study included a total of 90 patients (n = 30), randomized to receive: etoricoxib 90 mg, dexamethasone 4 mg, or no premedication (control group) 1 h before surgery. Paracetamol 500 mg was prescribed as rescue medication (RM). Check-ups were scheduled at 24 h, 48 h, and day 7 post-surgery. At each time point, pPS was assessed using the 5-point Likert scale. RM parameters, swelling, trismus, and the occurrence of adverse events were also recorded, and patients were instructed to rate the perceived pain on Visual Analogue Scale. RESULTS: In all the follow-up periods, data indicated significantly higher pPS scores in the preemptive medication groups when compared to the control group (p < 0.05). Both regimens delayed the first RM intake when compared to controls. In the etoricoxib group, a significantly lower total RM consumption was observed (p < 0.05). Dexamethasone significantly decreased swelling at each check-up and increased mouth opening at day 7 after the surgery (p < 0.05). CONCLUSIONS: Preemptive etoricoxib and dexamethasone elevate pPS after IMTM surgery. Etoricoxib improves RM parameters, while dexamethasone ameliorates the patient's postoperative functional ability. CLINICAL RELEVANCE: Preemptive etoricoxib and dexamethasone use may decrease patients' discomfort following the impacted mandibular third molar extraction. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05791721. Date of Registration: 28/03/2023 (retrospectively registered).

Chondroitin Sulphate-Chitosan polyelectrolyte complexes for etorocoxib transdermal delivery: in silico, in vitro and in vivo studies.

Rheumatoid arthritis (RA) is a chronic autoimmune disease which affects around 1% globally leading to joint inflammation and disability. Etorocoxib (ETR) is a potent COX-2 inhibitor traditionally used orally to alleviate RA induced inflammation, yet it causes hepatic side effects on prolonged use. This study aims for in silico optimization of ETR polyelectrolyte complex (PEC) utilizing chondroitin sulphate (CS) and chitosan (CH) for transdermal delivery to RA-inflamed joints with a synergistic anti-inflammatory action owing to CS. An artificial neural network (ANN) combined with 22 factorial design was used to optimize the PEC formula according to particle size (PS) and entrapment efficiency (%EE) by varying CS and CH concentrations. The optimum ETR PEC was incorporated in a gel and examined for its in vitro release, ex vivo permeation, in vivo inflammatory biomarkers, and histopathological evaluation in rats. The optimized formula (F3) with 0.1 CH% w/w and 0.5 CS %w/w showed a PS of 214.98 ± 17.24 nm, %EE 75.31 ± 1.67%, and enhanced in vitro release profile, ex vivo permeation and in vivo anti-inflammatory effect compared to ETR gel via suppressing the expression of IL-6, TNF-α, and TGF-ß pro-inflammatory cytokines as well as the additional anti-inflammatory effect of CS. In conclusion, ETR-PEC gel holds promise as transdermal therapy for managing RA-induced inflammation.

Ascorbic Acid Ameliorates Cardiac and Hepatic Toxicity Induced by Azithromycin-Etoricoxib Drug Interaction.

The complexity of prescribing safe and effective drug therapy is still challenging. Due to the increased number of medications taken by patients, the potential for drug-drug interactions has clinically important consequences. This study focuses on the potential drug-drug interaction between azithromycin and etoricoxib and the possibility of counteracting this adverse reaction by giving ascorbic acid intraperitoneally to male albino rats. Sixty adult male albino rats weighing 150-180 g were used. The rats were allocated into six equal groups. One group was a control, and the others were given azithromycin, etoricoxib, either alone or combination, with one group treated with ascorbic acid and the last group treated with the drug combination and ascorbic acid. Blood samples were collected for measuring AST, ALT, LDH, CK-MB, and troponin alongside antioxidant enzymes and histopathological examination for both liver and heart tissue. The results showed both hepatic and cardiac damage in azithromycin and etoricoxib groups represented by increasing levels of heaptoc enzymes (ALT, AST, LDH, CK-MB, and troponin) with declining antioxidant enzymes and elevation of malondialdehyde and the appearance of hepatic and cardiac toxicities. Upon administration, ascorbic acid ameliorated all the mentioned biochemical parameters. In conclusion, ascorbic acid has great antioxidant capacities and hepatic and cardiac ameliorative effects and can alleviate drug interaction toxicity.

Etoricoxib and celecoxib sensitive indomethacin-responsive headache disorders.

Indomethacin-responsive headaches encompass a group of disorders which include a subset of the trigeminal autonomic cephalalgias and other paroxysmal, often precipitated primary headaches. Many patients show a rapid therapeutic response to indomethacin, which is limited by intolerability. Etoricoxib and celecoxib, selective inhibitors of cyclo-oxygenase-2 (COX-2), spare gastroduodenal COX-1 activity and are less likely to cause gastrointestinal adverse effects than indomethacin. We report a case series of eight patients, seven who responded to etoricoxib and one patient who responded to celecoxib.

Fast and Sensitive HPLC-ESI-MS/MS Method for Etoricoxib Quantification in Human Plasma and Application to Bioequivalence Study.

Etoricoxib is a non-steroidal anti-inflammatory drug (NSAID) used to treat pain and inflammation. The objective of the current study was to develop a sensitive, fast and high-throughput HPLC-ESI-MS/MS method to measure etoricoxib levels in human plasma using a one-step methanol protein precipitation technique. A tandem mass spectrometer equipped with an electrospray ionization (ESI) source operated in a positive mode and multiple reaction monitoring (MRM) were used for data collection. The quantitative MRM transition ions were m/z 359.15 > 279.10 and m/z 363.10 > 282.10 for etoricoxib and IS. The linear range was from 10.00 to 4000.39 ng/mL and the validation parameters were within the acceptance limits of the European Medicine Agency (EMA) and Food and Drug Analysis (FDA) guidelines. The present method was sensitive (10.00 ng/mL with S/N > 40), simple, selective (K prime > 2), and fast (short run time of 2 min), with negligible matrix effect and consistent recovery, suitable for high throughput analysis. The method was used to quantitate etoricoxib plasma concentrations in a bioequivalence study of two 120 mg etoricoxib formulations. Incurred sample reanalysis results further supported that the method was robust and reproducible.

Synthesis of Copper Oxide-Based Nanoformulations of Etoricoxib and Montelukast and Their Evaluation through Analgesic, Anti-Inflammatory, Anti-Pyretic, and Acute Toxicity Activities.

Copper oxide nanoparticles (CuO NPs) were synthesized through the coprecipitation method and used as nanocarriers for etoricoxib (selective COX-2 inhibitor drug) and montelukast (leukotriene product inhibitor drug) in combination therapy. The CuO NPs, free drugs, and nanoformulations were investigated through UV/Vis spectroscopy, FTIR spectroscopy, XRD, SEM, and DLS. SEM imaging showed agglomerated nanorods of CuO NPs of about 87 nm size. The CE1, CE2, and CE6 nanoformulations were investigated through DLS, and their particle sizes were 271, 258, and 254 nm, respectively. The nanoformulations were evaluated through in vitro anti-inflammatory activity, in vivo anti-inflammatory activity, in vivo analgesic activity, in vivo anti-pyretic activity, and in vivo acute toxicity activity. In vivo activities were performed on albino mice. BSA denaturation was highly inhibited by CE1, CE2, and CE6 as compared to other nanoformulations in the in vitro anti-inflammatory activity. The in vivo bioactivities showed that low doses (5 mg/kg) of nanoformulations were more potent than high doses (10 and 20 mg/kg) of free drugs in the inhibition of pain, fever, and inflammation. Lastly, CE2 was more potent than that of other nanoformulations.

The effect of non-steroidal anti-inflammatory drugs with different mechanisms of action on the body temperature and cyclooxygenase pathway of the arachidonic acid cascade on the model of acute general cooling (air hypothermia) in rats.

NSAIDs are promising agents for preventing cold injury (frigoprotectors). The influence of prophylactic administration of the non-selective COX inhibitor diclofenac sodium (7 mg/kg) and the highly selective COX-2 inhibitor etoricoxib (5 mg/kg) on cyclooxygenase pathway biomarkers was studied on the model of acute general cooling (air hypothermia at -18 °С for 2 hours). Diclofenac completely prevented a decrease in body temperature, surpassing etoricoxib. In the liver of the rats immediately after cold exposure, the content of COX-1 was increased moderately and the content of COX-2 highly significantly. Very significantly, the level of PGE2 decreased, and the levels of PGF2α, especially PGI2 and TXB2, were elevated. In the blood serum, the level of COX-1 was decreased, and the changes in COX-2 and prostaglandins levels were similar to those in the liver. Diclofenac exerted a moderate effect towards the normalization of both COX isoforms in the liver, moderately increased the content of PGE2, and decreased - PGF2α and TXB2 without changing the level of PGI2. In serum, diclofenac reduced COX-1 level to subnormal values, and its effect on other biomarkers was similar to that in the liver, except for a moderate decrease in PGI2. Thus, diclofenac was inferior to etoricoxib, which normalized COX-1, COX-2, PGE2, and PGI2 in the liver and reduced the content of PGF2α and TXB2 in the liver to subnormal values. At the same time, in the blood serum, it decreased COX-1, COX-2, and PGE2 to subnormal values, normalized PGF2α, and PGI2, and significantly reduced TXB2. The opposite degree of intensity of the influence of diclofenac and etoricoxib on the cyclooxygenase pathway and body temperature indicates a dissociation of anti-inflammatory and frigoprotective activity. Inhibition of oxidative stress is not determinative for the frigoprotective activity of NSAIDs since diclofenac, despite the weaker influence on the content of 8-isoprostane in the liver, still exerts the maximum frigoprotective activity.

An experimental study of rosuvastatin's analgesic effect and its interaction with etoricoxib, tramadol, amlodipine, and amitriptytline in albino mice.

Background: Statins are the mainstay for the treatment of dyslipidemia. Recently, rosuvastatin has also been demonstrated to possess analgesic properties in animal studies. The present study has been planned to further confirm the analgesic activity of rosuvastatin, etoricoxib, tramadol, amlodipine, and amitriptyline and study the interaction of rosuvastatin with the above-mentioned analgesics. The objective of the study was to confirm the analgesic activity of rosuvastatin and determine the minimum analgesic dose of rosuvastatin, etoricoxib, tramadol, amlodipine and amitriptyline and to study the analgesic effect of combination of subanalgesic doses of rosuvastatin with sub-analgesic doses of etoricoxib, tramadol, amlodipine, and amitriptyline. Method: After IAEC approval, the study was carried out in albino mice in two phases. In phase I, the analgesic effect of rosuvastatin, etoricoxib, tramadol, amlodipine, and amitriptyline was confirmed by using tail-flick and writhing methods. In phase II, analgesic effect of combinations of subanalgesic dose of rosuvastatin with subanalgesic dose of etoricoxib, tramadol, amlodipine, and amitriptyline was studied. Results: Minimal analgesic dose of rosuvastatin, etoricoxib, tramadol, amlodipine, and amitriptyline was observed as 5, 20, 10, 5, and 10 mg/kg, respectively. In phase II, combination of subanalgesic dose of rosuvastatin 2.5 mg/kg with subanalgesic doses of etoricoxib (10 mg/kg), tramadol (5 mg/kg), amlodipine (2.5 mg/kg), and amitriptyline (5 mg/kg), demonstrated synergistic analgesic activity. Conclusion: Rosuvastatin exerts dose-dependent analgesic activity that is synergistic to that of etoricoxib, tramadol, amlodipine, and amitriptyline. If established in clinical studies as well, this finding can lead to the reduction of analgesic dosing in patients already on statins.

Etoricoxib-induced fixed drug eruption: Report of seven cases.

BACKGROUND: Fixed drug eruption (FDE) is a characteristic form of intraepidermal CD8+ T cell-mediated drug reaction, with repeated appearance of isolated or multiple skin lesions in the same location after receiving the offending drug. Non-steroidal anti-inflammatory drugs (NSAID) are the most common cause. Selective inhibitors of inducible cyclooxygenase 2 (COX-2) provoke a lesser degree of allergic or idiosyncratic adverse reactions than conventional NSAID, but they can cause skin reactions of variable severity. OBJECTIVE: Etoricoxib has been related to a variety of unusual skin reactions, including several reports of FDE. METHODS: We perfomed epicutaneous test to diagnose patients with suspected etoricoxib fixe drug rash due to clinical features and reproducibility on at least two occasions. RESULTS: We present seven new cases of etoricoxib-induced fixed drug eruption, with a diagnosis based on clinical presentation. This diagnosis was confirmed by an etoricoxib-positive lesional patch test in six cases and by a positive low-dose oral challenge in the other one. Two patients showed negative patch tests with celecoxib (10% in pet.) on the residual lesions, and oral tolerance was confirmed in one. CONCLUSION: To our knowledge, this is the largest series on FDE induced by etoricoxib reported to date.

Development and Evaluation of Repurposed Etoricoxib Loaded Nanoemulsion for Improving Anticancer Activities against Lung Cancer Cells.

In the present work, novel modality for lung cancer intervention has been explored. Primary literature has established the potential role of cyclooxygenase-2 (COX-2) inhibitor in regression of multiple forms of carcinomas. To overcome its poor water solubility and boost anticancer activity, etoricoxib (ETO) was chosen as a therapeutic candidate for repurposing and formulated into a nanoemulsion (NE). The prepared ETO loaded NE was characterized for the surface charge, droplet size, surface morphology, and in vitro release. The optimized ETO loaded NE was then investigated for its anticancer potential employing A549 lung cancer cell line via cytotoxicity, apoptotic activity, mitochondrial membrane potential activity, cell migration assay, cell cycle analysis, Caspase-3, 9, and p53 activity by ELISA and molecular biomarker analysis through RT-PCR test. The developed ETO-NE formulation showed adequate homogeneity in the droplet size distribution with polydispersity index (PDI) of (0.2 ± 0.03) and had the lowest possible droplet size (124 ± 2.91 nm) and optimal negative surface charge (-8.19 ± 1.51 mV) indicative of colloidal stability. The MTT assay results demonstrated that ETO-NE exhibited substantial anticancer activity compared to the free drug. The ETO-NE showed a substantially potent cytotoxic effect against lung cancer cells, as was evident from the commencement of apoptosis/necrotic cell death and S-phase cell cycle arrests in A549 cells. The study on these molecules through RT-PCR confirmed that ETO-NE is significantly efficacious in mitigating the abundance of IL-B, IL-6, TNF, COX-2, and NF-kB as compared to the free ETO and control group. The current study demonstrates that ETO-NE represents a feasible approach that could provide clinical benefits for lung cancer patients in the future.

Does low dose of etoricoxib play pre-emptive analgesic effect in third molar surgery? A randomized clinical trial.

BACKGROUND: How to prevent pain after the extraction of impacted teeth is a serious challenge for all patients. The purpose of this clinical trial was to investigate whether pre-emptive low dose of etoricoxib can reduce postoperative pain in patients undergoing third molars surgery. METHODS: Patients were randomised to receive etoricoxib 60 mg or placebo 30 min before surgery. Post-operative pain was recorded using a visual analogue scale during 24 h within the post-operative period. The total dose of ibuprofen rescue intake was recorded. Kaplan-Meier curves and log-rank analyses were used to evaluate the proportion of patients without rescue analgesic. RESULTS: Scores for the post-operative pain in the etoricoxib group were significantly lower than those in the placebo group during first 12 h (p < 0.05). The number of patients without analgesic rescue medication was significantly lower in the etoricoxib group than in the placebo group. The average amount of rescue medication in the etoricoxib group (0.4 ± 0.9 dose) was lower than that in the placebo group (1.1 ± 0.9 doses, p = 0.004). Etoricoxib resulted in the long-term survival of patients without rescue analgesic (p < 0.001). CONCLUSIONS: This study revealed that etoricoxib has a substantial pre-emptive analgesic effect, resulting in the reduced use of analgesics after third molar removal. TRIAL REGISTRATION: Registered on ChiCTR1900024503. Date of Registration: 13/07/2019.

The effect of etoricoxib versus diclofenac on blood pressure in hypertensive patients.

OBJECTIVE: To compare the effect of etoricoxib, a selective cyclooxygenase-2 inhibitor, with diclofenac, a non-selective nonsteroidal anti-inflammatory drug, on blood pressure in hypertensive patients. METHODS: The prospective observational study was conducted at Al-Hussein Medical City, Karbala, Iraq, from July 2018 to March 2019, and comprised patients with hypertension already on antihypertensive treatment. The subjects were divided into 2 equal groups. Those in group 1 received etoricoxib, while patients in group 2 received diclofenac sodium. They were followed up for 2 weeks. Pulse rate, blood pressure and renal indices were noted and compared between the groups. Data was analysed using 2-tailed t-test for continuous variables, and chi-square test for categorial ones. RESULTS: Of the 100 subjects, there were 50(50%) in group 1 with a mean age of 48.7±14.9 years including 15(30%) males, and the remaining 50(50%) were in group 2 with a mean age of 51.9 ± 13.4 years including 14(28%) males (p>0.05). The blood pressure was elevated above the normal upper limit in 16(32%) in group 1 patients compared to 6(12%) in group 2 (p=0.015). The mean rise in systolic blood pressure in group 1 was 16.2±15mmHg compared to 8.5±11 in group 2 (p=0.004), and the mean rise in diastolic blood pressure was 7.1±9 compared to 2.4±7 in the two groups, respectively (p=0.004). The mean increase in pulse rate was 8.1±16 in group 1 compared to 6.2±14 in group 2 (p=0.529). There was no significant change in renal indices between the two groups (p>0.05). CONCLUSIONS: Etoricoxib was found to be significantly more effective than diclofenac on raising blood pressure of hypertensive patients. With respect to pulse rate and renal indices, the two drugs were not significantly different.

The association between nonsteroidal anti-inflammatory drugs and skin cancer: Different responses in American and European populations.

OBJECTIVE: To conduct a comprehensive systematic meta-analysis investigating the association of nonsteroidal anti-inflammatory drugs (NSAIDs) and their subtypes with skin cancer (SC) and its subclasses (basal cell carcinoma BCC; squamous cell carcinoma SCC; melanoma; nonmelanoma skin cancer NMSC) in general, American and European populations. METHODS: PubMed, Embase, the Cochrane Library, the China National Knowledge Infrastructure and ClinicalTrials.gov were searched up to 24 February 2019. Pooled effect sizes and 95% confidence intervals were used to estimate associations. RESULTS: Results based on 26 original studies including 223,619 cases and 1,398,507 controls showed both NSAIDs and nonselective Cyclooxygenase (COX) inhibitors to be statistically significantly associated with a reduced risk of SC, BCC, SCC and NMSC but not with melanoma. Conversely, no association was observed between selective Cyclooxygenase 2 (COX-2) inhibitors and SC or its subclasses. Further subgroup analysis showed that the results analyzed for American populations were almost the same as those for the general population. For European populations, neither NSAIDs nor its subtypes correlated significantly with susceptibility to SC or its subclasses. CONCLUSIONS: The use of NSAIDs might reduce the risk of SC, but many factors including study population, drug subtype, and disease subclass affect the significance of the association.

Rapid quantitative analysis of etoricoxib in human plasma by UPLC-MS/MS and application to a pharmacokinetic study in Chinese healthy volunteers.

A selective and sensitive liquid chromatography-tandem mass spectrometry method was developed for simultaneous determination of etoricoxib in human plasma. Chromatography was performed on an Acquity UPLC HSS T3 column (1.8 µm, 50 × 2.1 mm), with a flow rate of 0.600 mL/min, using a gradient elution with acetonitrile and water which contained 2 mm ammonium acetate as the mobile phase. Detection was carried out on Triple QuadTM 5500 mass spectrometer under positive-ion multiple reaction monitoring mode. The respective mass transitions used for quantification of etoricoxib and etoricoxib-d3 were m/z 359.0 → 280.1 and m/z 362.0 → 280.2. Calibration curves were linear over the concentration range of 5-5000 ng/mL. The validated method was applied in the pharmacokinetic study of etoricoxib in Chinese healthy volunteers under fed and fasted conditions. After a single oral dose of 120 mg, the main pharmacokinetic parameters of etoricoxib in fasted and fed groups were respectively as follows: peak concentration, 2364.78 ± 538.01 and 1874.55 ± 367.90 ng/mL; area under the concentration-time curve from 0 to 120 h, 44,605.53 ± 15,266.66 and 43,516.33 ± 12,425.91 ng h/mL; time to peak concentration, 2.00 and 2.50 h; and half-life, 24.08 ± 10.06 and 23.64± 6.72 h. High-fat food significantly reduced the peak concentration of etoricoxib (p = 0.001) but had no effect on the area under the concentration-time curve.

PEG-PLGA- hybrid nanoparticles loaded with etoricoxib - phospholipid complex for effective treatment of inflammation in rat model.

The aim of the present study was to increase the bioavailability of the etoricoxib by making PEG-PLGA-Hybrid nanoparticles using emulsion solvent evaporation method. Then the prepared nanoparticles were further characterised using TEM, particle size, PDI, zeta potential, encapsulation efficiency and drug release study. Lipid (Phospholipon 90-G) and drug thermal behaviour were studied using DSC, TGA. The results of optimised formulation of Particle size, PDI and zeta potential was found 216.6 ± 4.0 nm, 0.24 ± 0.19 and +36.3 ± 1.9 mV. Encapsulation efficiency was found in the range of 77.15% w/v to 93.88% w/v. In-vivo study shows that the optimised formulation at a particular dose decreases the swelling index and number of writhes. Stability study indicated that the nanoparticles can be stored at a temperature of 4 ± 2 °C/60 ± 5% RH in well-closed container, away from heat and damp places. The prepared formulation has significantly increased the bioavailability of etoricoxib via oral administration.