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The structures of three 1:1 cocrystal forms of etoricoxib {ETR; systematic name: 5‐chloro‐2‐(6‐methylpyridin‐3‐yl)‐3‐[4‐(methylsulfonyl)phenyl]pyridine, C18H15ClN2O2S} have been synthesized and characterized by single‐crystal X‐ray diffraction; these are etoricoxib–benzoic acid (1/1), C18H15ClN2O2S·C7H6O2 (ETR–Bz), etoricoxib–4‐fluorobenzoic acid (1/1), C18H15ClN2O2S·C7H5FO2 (ETR–PFB), and etoricoxib–4‐nitrobenzoic acid (1/1), C18H15ClN2O2S·C7H5NO4 (ETR–PNB). Powder X‐ray diffraction and thermal differential scanning calorimetry–thermogravimetry (DSC–TG) techniques were also used to characterize these multicomponent systems. Due to the influence of the corresponding acids, ETR shows different conformations. Furthermore, the energetic contributions of the supramolecular motifs have been established by energy framework studies of the stabilizing interaction forces and are consistent with the thermal stability of the cocrystals. [ABSTRACT FROM AUTHOR]

Multimodal analgesia is defined as using several drugs or techniques simultaneously to target different pain pathways or receptors to avoid pain propagation. This study evaluated the pharmacokinetic profile and comparative bioavailability of etoricoxib 90 mg and tramadol 50 mg dosing alone (reference drugs) or in a novel fixed‐dose combination (test drug) under fasting conditions in Mexican healthy volunteers. This was a randomized, open‐label, 3‐way, crossover, single‐dose, prospective, and longitudinal study with a 14‐day washout period. Eligible subjects were healthy Mexican adult volunteers. The drugs were dosing orally, according to the randomization sequence, after 10 hours of fasting and 4 hours before breakfast with 250 mL of water at room temperature. Serial blood samples were collected before and after dosing, both drugs were quantified using high‐performance liquid chromatography coupled with tandem mass spectrometry. Forty‐two subjects were enrolled and 38 completed the study (28 men and 14 women, mean age 25.2 years, mean weight 66.6 kg). Test products were considered to have comparative bioavailability if confidence intervals of natural log‐transformed for (maximum plasma drug concentration (Cmax), (area under the plasma drug concentration‐time curve form 0 up to last sampling time (AUC0‐t), and (area under the plasma drug concentration‐time curve from 0 up to infinity (AUC0‐∞) data were within the range of 80%‐125%. Non‐serious adverse events were observed. The results demonstrate that the pharmacokinetic profile and bioavailability of the etoricoxib/tramadol fixed‐dose combination are comparable to those of the reference products. [ABSTRACT FROM AUTHOR]

Objective: The effect of Etoricoxib (ETOR) on the link between blood glucose and seizure prevention in chemo-convulsive rats was investigated in this study. Methods: Pentylenetetrazol (PTZ-105 mg/kg i.p.) at the CD97 dosage was administered to rats to cause seizures. ETOR (10 mg/kg p.o.) was administered for two weeks prior to seizure induction. On the 14th day, the animals were exposed to chemo convulsions, and the efficiency of ETOR in lowering clonus-type chemo convulsions (CC) as well as blood glucose levels were assessed. Morphometric analysis and chimney tests were performed to evaluate ETOR's neurotoxic profile. Actophotometer, rotarod, and hole board tests were employed for behavioral analysis. Results: When compared to control mice, pretreatment with ETOR (10 mg/kg p.o) resulted in a substantial delay in the onset of CC (P<0.05) and duration of CC (P<0.01). Acute ETOR treatment also considerably lowered blood glucose levels. The chimney test findings show that it has no effect on motor control and is not neurotoxic to the animals. Conclusion: Behavioral tests also demonstrated that, except for the diazepam-treated groups, no significant changes in muscle coordination, locomotion, or apprehensive behavior were detected in all experimental animals. Finally, the primary findings of this study showed that the PTZ group had considerably greater levels of hyperglycemia, which is reflected in the rat's early onset and longer duration of chemo-convulsions. However, ETOR medication reduced high blood glucose levels as well as the onset and duration of seizures, indicating ETOR's impact on blood glucose reduction and the relationship between blood glucose and seizure responses. [ABSTRACT FROM AUTHOR]

Background: The term "gout" refers to a broad clinical spectrum of diseases, including common and complex forms of arthritis, that affect multiple joints in a patient due to an elevated serum urate concentration. Purpose: The study aims to compare the efficacy and safety of selective cyclooxygenase-2 (COX-2) inhibitors and non-selective nonsteroidal anti-inflammatory drugs (NSAIDs) in the treatment of acute gout, as well as to conduct a meta-analysis on safety. Methodology: As of December 2021, the literature search was conducted using authorised electronic databases such as PubMed, Embase, Web of Science, and the Cochrane Library. Results: There were seven investigations included in this study's findings. Three COX-2 inhibitors, etoricoxib, celecoxib, and meloxicam, were reportedly compared to indomethacin or diclofenac. Four hours after the initial dose, 120 mg of etoricoxib reduces pain and inflammation by diminishing erythema. At higher dosages, celecoxib is more effective than at lower doses. Meloxicam has the same efficacy as NSAIDs. The subgroup analysis revealed that the risk of adverse events was 8.0% lower in the COX-2 inhibitors group than in the non-selective NSAIDs group (risk ratio = 0.92, 95% confidence interval = 0.60 to 0.40, p -value = 0.5). Conclusion: Etoricoxib, a COX-2 inhibitor, has a more potent effect and may be more effective than non-selective NSAIDs. COX-2 inhibitors are more well tolerated and reduce the risk of adverse gastrointestinal events more effectively than non-selective NSAIDs. In the treatment of gout, non-selective NSAIDs may be a suitable alternative to COX-2 inhibitors. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background. Nonsteroidal anti-inflammatory drugs (NSAIDs) are an important drug class for the treatment of osteoarthritis (OA). Despite existing studies on the bioequivalence of original and generic NSAIDs, comparative studies related to their clinical efficacy and safety are limited. The purpose of the study was to compare the clinical efficacy and safety of the original and generic forms of etoricoxib in patients with knee OA. ­Materials and ­methods. In an open, comparative, randomized, multicenter study, 150 patients with knee OA were examined: group I — 50 persons who received the original etoricoxib (60 mg/d for 10 days), groups II and III — 50 subjects each who received generic etoricoxib (60 mg/d for 10 days). The effectiveness of the treatment was evaluated using the four-component visual analog scale (VAS), the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and the Lequesne index before the start of therapy and on the 10th day. Assessment of tolerability and safety was studied by controlling adverse events based on clinical and laboratory indicators. Results. The use of the original and generic forms of etoricoxib in patients with knee OA led to positive dynamics of pain syndrome and functional activity, while the dynamics of indices were the greatest in the case of using the ori­ginal etoricoxib (VAS: group I — 50.0 [35.4–60.0] %, group II — 29.1 [16.7–55.0] % and III — 28.6 [14.3–33.3] %). The most pronounced positive dynamics of the pain syndrome against the background of taking the original etoricoxib compared to the generic forms was registered in the subgroup of patients with severe knee pain (VAS > 60 mm). The use of all forms of etorico­xib was safe and did not lead to serious clinical side effects or clinically signi­ficant changes in laboratory blood parameters. The hi­ghest rates of satisfaction with the treatment by patients and physicians were observed in the case of the original etoricoxib use. Conclusions. The use of the original etoricoxib in patients with knee OA, especially in the presence of severe pain syndrome (VAS > 60 mm) is the most justified and safe.

An ultra-performance liquid chromatography with photodiode array (UPLC-PDA) UV detection method was developed here for the first time for simple, rapid, selective and sensitive quantification of the commonly prescribed selective cyclooxygenase-2 (COX-2) inhibitor etoricoxib in low plasma volumes (50 μL). The method includes protein precipitation followed by liquid–liquid extraction, evaporation and reconstitution. A gradient mobile phase of 75:25 going to 55:45 (v/v) water:acetonitrile (1 mL/min flow rate) was applied. Total run time was 8 min, representing a significant improvement relative to previous reports. Excellent linearity (r2 = 1) was obtained over a wide (0.1–12 µg/mL) etoricoxib concentration range. Short retention times for etoricoxib (4.9 min) and the internal standard trazodone (6.4 min), as well as high stability, recovery, accuracy, precision and reproducibility, and low etoricoxib LOD (20 ng/mL) and LOQ (100 ng/mL), were achieved. Finally, the method was successfully applied to a pharmacokinetic study (single 20 mg/kg orally administered etoricoxib mini-capsule) in rats. In conclusion, the advantages demonstrated in this work make this analytical method both time- and cost-efficient for drug monitoring in pre-clinical/clinical settings. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Fixed drug eruption (FDE) is a well-recognized, non-immediate, drug hypersensitivity reaction, often attributed to the use of various medications, most commonly non-steroidal anti-inflammatory drugs (NSAIDs) and antibiotics. Cross-reactivity between related NSAIDs in FDE has been reported, but among chemically unrelated NSAIDs, is rare. Herein, we present a rare well-documented case where a patient initially displayed tolerance to etoricoxib after experiencing a nimesulide-induced FDE. Subsequently, the patient developed an etoricoxib-induced FDE, accompanied by the development of bullous lesions. This case report and the literature review on comparable FDE occurrences shed light on the intricate nature of FDEs, suggesting the possibility of cross-reactivity between chemically related and unrelated NSAIDs or the emergence of new drug-specific T cells without cross-reactivity after multiple exposures to a drug in a susceptible patient. Our case underscores the importance of increased awareness and vigilance among both physicians and patients in the realm of personalized medicine. Further research is needed to unravel the intricate mechanisms behind these drug eruptions, improve diagnostic approaches, and enhance patient care. [ABSTRACT FROM AUTHOR]

Etoricoxib (ETO) is a selective cyclooxygenase‐2 inhibitor, used as a nonsteroidal anti‐inflammatory drug. In this study, a detailed investigation was conducted on the degradation behavior of ETO under acidic, basic, neutral, photolytic, oxidative, and thermal degradation conditions as per the International Conference on Harmonization (ICH) guideline Q1A (R2). A gradient "ultra‐performance liquid chromatography (UPLC)" method was developed for separating the degradation products formed under various degradation conditions along with process‐related impurities. Acquity BEH phenyl column was used for the separation of analytes and 0.1% formic acid in water and 0.05% formic acid in acetonitrile:methanol (8:2 %v/v) were used as mobile phase‐A and mobile phase‐B. A major degradant namely, N‐oxide impurity was observed in oxidative degradation along with two minor degradants where N‐oxide was confirmed based on LC‐mass spectrometry (LC‐MS) studies. Further, the major degradant was enriched and isolated using preparative HPLC and the conformation of the N‐oxide impurity was established using nuclear magnetic resonance techniques including two‐dimensional studies and high‐resolution MS. In addition, the method for related substances by UPLC has been validated by considering a major degradant, namely N‐oxide along with process‐related impurities as per the ICH guidelines validation parameters. [ABSTRACT FROM AUTHOR]

Abstract The multivariate models that are used for spectral data analysis have many beneficial applications, and one of the important applications is the analysis of drugs and their impurities. Three Chemometrically-assisted spectrophotometric models have been proposed and validated. The proposed models are Partial Least Squares (PLS), Artificial Neural Networks (ANN), and Multivariate Curve Resolution-Alternating Least Squares (MCR-ALS). The advanced chemometric models were applied to resolve the significantly overlapping spectra of Etoricoxib (ETO) and Paracetamol (PCM), along with impurities of PCM namely; P-aminophenol (PAP) and P-hydroxy acetophenone (PHA). The proposed models succeeded in simultaneously analyzing the mixture of ETO and PCM along with the impurities of PCM. So, the proposed techniques can be used without requiring a separation step in the analysis of pharmaceutical formulation. Moreover, no significant differences were found when the results of the suggested and published chemometric models were compared statistically with the reported HPLC method.

Background. Nonsteroidal anti-inflammatory drugs (NSAIDs) are an important drug class for the treatment of osteoarthritis (OA). Despite existing studies on the bioequivalence of original and generic NSAIDs, comparative studies related to their clinical efficacy and safety are limited. The purpose of the study was to compare the clinical efficacy and safety of the original and generic forms of etoricoxib in patients with knee OA. Materials and methods. In an open, comparative, randomized, multicenter study, 150 patients with knee OA were examined: group I - 50 persons who received the original etoricoxib (60 mg/d for 10 days), groups II and III - 50 subjects each who received generic etoricoxib (60 mg/d for 10 days). The effectiveness of the treatment was evaluated using the four-component visual analog scale (VAS), the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and the Lequesne index before the start of therapy and on the 10th day. Assessment of tolerability and safety was studied by controlling adverse events based on clinical and laboratory indicators. Results. The use of the original and generic forms of etoricoxib in patients with knee OA led to positive dynamics of pain syndrome and functional activity, while the dynamics of indices were the greatest in the case of using the original etoricoxib (VAS: group I - 50.0 [35.4-60.0] %, group II - 29.1 [16.7-55.0] % and III - 28.6 [14.3-33.3] %). The most pronounced positive dynamics of the pain syndrome against the background of taking the original etoricoxib compared to the generic forms was registered in the subgroup of patients with severe knee pain (VAS > 60 mm). The use of all forms of etoricoxib was safe and did not lead to serious clinical side effects or clinically significant changes in laboratory blood parameters. The highest rates of satisfaction with the treatment by patients and physicians were observed in the case of the original etoricoxib use. Conclusions. The use of the original etoricoxib in patients with knee OA, especially in the presence of severe pain syndrome (VAS > 60 mm) is the most justified and safe. [ABSTRACT FROM AUTHOR]

The multivariate models that are used for spectral data analysis have many beneficial applications, and one of the important applications is the analysis of drugs and their impurities. Three Chemometrically-assisted spectrophotometric models have been proposed and validated. The proposed models are Partial Least Squares (PLS), Artificial Neural Networks (ANN), and Multivariate Curve Resolution-Alternating Least Squares (MCR-ALS). The advanced chemometric models were applied to resolve the significantly overlapping spectra of Etoricoxib (ETO) and Paracetamol (PCM), along with impurities of PCM namely; P-aminophenol (PAP) and P-hydroxy acetophenone (PHA). The proposed models succeeded in simultaneously analyzing the mixture of ETO and PCM along with the impurities of PCM. So, the proposed techniques can be used without requiring a separation step in the analysis of pharmaceutical formulation. Moreover, no significant differences were found when the results of the suggested and published chemometric models were compared statistically with the reported HPLC method. [ABSTRACT FROM AUTHOR]

This study aimed to formulate and evaluate a floating raft system for the co-delivery of etoricoxib (ETO) and famotidine (FAM) using a combination of glucomannan with natural/semi-synthetic polysaccharides. Formulation variables affect gelation lag time (GLT), floating lag time (FLT), and release percentage of drugs after 1–8 h, Stability, and viscosity parameters were evaluated. In vivo X-ray studies, followed by the pharmacokinetic study, were performed on human volunteers. Formulations exhibited pseudoplastic behavior for ease of swallowing. The optimum raft system (ORS) comprised 1% Na alginate, 0.1% Low Methoxyl (LM) pectin, 0.8% Konjac glucomannan (KGL), 1% Precirol, and 1% CaCO3. ORS exhibited rapid GLT and FLT (around 42 and 8 sec respectively) in 0.1 N HCl as well as controlled release of ETO (15% in 1 h and 82% in 8 h) and FAM (29% in 1 h and 85% in 8 h). Formulation stability with the absence of any drug-excipient interactions was observed. The X-ray imaging showed a promising buoyancy ability for approximately 8 h. Compared with marketed products, ORS showed superior relative bioavailability for both drugs. These findings revealed the successful preparation of a promising raft system with improved dual drug delivery. [ABSTRACT FROM AUTHOR]

Determining the influence of environmental factors on the stability of drugs is very helpful when choosing excipients, storage conditions or packaging materials. In addition, information about possible toxic degradation products enables detecting and avoiding the harmful side effects of the drug. We used the thin-layer chromatographic-densitometric procedure for the assay of five coxibs, conducted degradation studies in various environments and at different temperatures along with the determination of pharmacokinetic parameters. The results were subjected to chemometric analysis, to investigate and visualize the similarities and differences of the studied coxibs. Samples of the tested drug were also analyzed by UPLC-MS/MS in order to identify degradation products, and determine possible drug degradation pathways. Using the human liver cancer HepG2 cell line, the hepatotoxic effect of the degradation products was also determined. It was observed that all substances were relatively stable under the analyzed conditions and degraded more in acidic than alkaline environments. Robenacoxib is the drug that decomposes the fastest, and cimicoxib turned out to be the most stable. Robenacoxib also showed significant hepatotoxicity at the highest tested concentration, which correlates with the high degree of its degradation, and the probable formation of a more hepatoxic product. The obtained mass spectra of compounds formed as a result of hydrolysis of the protonated drug leading to the formation of several product ions, which enabled us to propose probable degradation pathways. [ABSTRACT FROM AUTHOR]

Etoricoxib is a non-steroidal anti-inflammatory drug with high selectivity for cyclooxygenase 2 (COX-2), exerting a pronounced anti-inflammatory effect with fewer adverse events when compared to COX-1 inhibitors. The present study aimed to evaluate the bioequivalence between two etoricoxib-coated tablet formulations to meet regulatory requirements for a branded generic product registration in Brazil. A crossover study with an open-label, randomized design and a single-dose regimen with two treatments and two periods was conducted on healthy Brazilians of both genders. Subjects randomly received a single dose of a 90 mg etoricoxib coated tablet of test product Xumer® 90 mg (Adium S.A.) and the reference product Arcoxia® 90 mg (Merck Sharp & Dohme Farmacêutica Ltda.) under fasting conditions separated by a 14-day period. Blood samples were collected sequentially for up to 96 h following drug administration, and the concentrations of etoricoxib in plasma were determined using a validated UPLC-MS/MS method. Pharmacokinetic parameters were computed utilizing non-compartmental analysis methods. A total of 32 healthy subjects were enrolled, and 25 subjects completed the study. Geometric mean ratios (90% confidence intervals) for Cmax, AUC0-t, and AUC0-inf were 103.98% (95.63–113.06), 96.82% (91.82–102.09), and 95.79% (90.70–101.16), respectively. In accordance with regulatory standards, the test formulation (Xumer® 90 mg) has been deemed bioequivalent to the reference product (Arcoxia® 90 mg). As a result, these formulations can be considered interchangeable in clinical practice, with both proving to be safe and well-tolerated. The need for in vivo testing for the Xumer® 60 mg strength was waived due to the proportional similarity of the formulations and the similar in vitro dissolution profiles observed across the various strengths. [ABSTRACT FROM AUTHOR]

Non-steroidal anti-inflammatory drugs (NSAIDs) have recently been considered promising agents for the prevention and treatment of cold injuries. The results of previous studies demonstrate a distinct frigoprotective effect of diclofenac sodium and etoricoxib. The aim of the study: to assess the impact of diclofenac sodium and etoricoxib, as the most effective frigoprotectors among NSAIDs, on coagulation indicators during the most acute phase of cold injuries using an acute model of general cooling in rats. Materials and Methods: The experiment was carried out using 41 outbreed male rats weighing 310±10 g. Cold injury was induced by acute general cooling (exposure to -18 °C for 2 hours). Diclofenac sodium (7 mg/kg) and etoricoxib (5 mg/kg) were administered intragastrically 30 minutes before the onset of cold exposure. Rectal temperature was measured before and after cold exposure. Immediately after exposure, plasma was used to determine prothrombin time (PT), thrombin time (TT), activated partial thromboplastin time (APTT), fibrinogen levels, and in blood serum - the residual amount of prothrombin, thrombin, fibrinogen, as well as D-dimer using species-specific immunoenzymatic analysis kits. Results: Etoricoxib and especially diclofenac sodium significantly reduced the degree of hypothermia (rectal temperature decreased by 1.3 % and 1.9 %, respectively, compared to a 5.4 % decrease in the control group, p<0.05). In the acute phase of cold injury in the untreated control group, there was a significant increase in D-dimer (by 2.7 times) and fibrinogen content (by 1.9 times) in blood serum, alongside a 21.7 % increase in thrombin time, indicating a heightened risk of thrombus formation and DIC syndrome development. The other coagulation indicators did not show significant changes. Both diclofenac sodium and etoricoxib significantly reduced elevated D-dimer and serum fibrinogen, normalizing thrombin time and indicating an antithrombotic effect. There was no significant difference in the effect of both NSAIDs on blood coagulation status. Conclusions: The acute phase of cold injury demonstrates a dangerous shift in blood coagulation towards thrombus formation and DIC syndrome development. Prophylactic use of diclofenac sodium and, to a lesser extent, etoricoxib displays an anti-hypothermic effect, reducing the risk of thrombosis and DIC syndrome. This proves the expediency of using these NSAIDs for acute cold injury. [ABSTRACT FROM AUTHOR]