Doses Of Celecoxib Research Articles

A single, maximal dose of celecoxib, ibuprofen, or flurbiprofen does not reduce the muscle signalling response to plyometric exercise in young healthy adults.

Non-steroidal anti-inflammatory drugs (NSAIDs) possess analgesic and anti-inflammatory properties by inhibiting cyclooxygenase (COX) enzymes. Conflicting evidence exists on whether NSAIDs influence signaling related to muscle adaptations and exercise with some research finding a reduction in muscle protein synthesis signaling via the AKT-mTOR pathway, changes in satellite cell signaling, reductions in muscle protein degradation, and reductions in cell proliferation. In this study, we determined if a single maximal dose of flurbiprofen (FLU), celecoxib (CEL), ibuprofen (IBU), or a placebo (PLA) affects the short-term muscle signaling responses to plyometric exercise. This was a block randomized, double-masked, crossover design, where 12 participants performed four plyometric exercise bouts consisting of 10 sets of 10 plyometric jumps at 40% 1RM. Two hours before exercise, participants consumed a single dose of celecoxib (CEL 200mg), IBU (800mg), FLU (100mg) or PLA with food. Muscle biopsy samples were collected before and 3-h after exercise from the vastus lateralis. Data were analyzed using a repeated measures (RM) ANOVA, ANOVA, or a Friedman test. Significance was considered at p < 0.05. We found no treatment effects on the mRNA expression of PTSG1, PTSG2, MYC, TBP, RPLOP, MYOD1, Pax7, MYOG, Atrogin-1, or MURF1 (all, p > 0.05). We also found no treatment effects on AKT-mTOR signaling or MAPK signaling measured through the phosphorylation status of mTORS2441, mTORS2448, RPS6 235/236, RPS 240/244, 4EBP1, ERK1/2, p38 T180/182 normalized to their respective total abundance (all, p > 0.05). However, we did find a significant difference between MNK1 T197/202 in PLA compared to FLU (p < .05). A single, maximal dose of IBU, CEL, or FLU taken prior to exercise did not affect the signaling of muscle protein synthesis, protein degradation, or ribosome biogenesis three hours after a plyometric training bout.

Assessing the efficacy of celecoxib after tonsillectomy and/or adenoidectomy: A systematic review and meta-analysis of randomised control trials.

Tonsillectomy and adenoidectomy are common surgical procedures that cause persistent pain, bleeding, and functional limitations. We aimed to investigate the efficacy of celecoxib compared with a placebo for managing post-tonsillectomy or adenoidectomy pain and other adverse events. Systematic review and meta-analysis. We conducted a systematic literature search in the PubMed, Cochrane, and Google Scholar databases from inception until July 2023. Dichotomous outcomes have been reported as risk ratios (RR) while continuous outcomes were reported using mean differences (MD). A funnel plot was drawn to investigate publication bias. From 1394 records identified, 6 randomised double-blind trials comprising 591 participants undergoing tonsillectomy and/or adenoidectomy were eligible for inclusion. A high dose (400 mg) of celecoxib was effective in decreasing the pain score for 'worst pain' after the procedure (MD: -10.98, [95% CI: -11.53, -10.42], p < .01, I2 = 0%) while a low dose (200 mg) was not significantly effective (p = 0.31). For managing other outcomes such as vomiting (RR: 1.37 [95% CI: 0.69, 2.68], p = 0.37, I2 = 67%), diarrhoea (RR: 1.41, [95% CI: 0.75, 2.64], p = .29, I2 = 42%), dizziness/drowsiness (RR: 0.90, [95% CI: 0.71, 1.15], p = .48, I2 = 0%), functional recovery time (p = .74), and headache (p = .91), there was no significant difference between the group on celecoxib and the placebo group regardless of dosage. Finally, there was no significant difference (RR: 1.02, [95% CI: 0.91, 1.15], p = .69, I2 = 0%) in the effect of the intervention on minimum bleeding, moderate bleeding, and profuse bleeding. This meta-analysis provides robust evidence pooled from high-quality trials and raises questions about the efficacy of celecoxib for tonsillectomy and/or adenoidectomy, challenging existing perceptions.

Efficacy of Celecoxib and Naproxen Sodium After Non-Surgical Extraction of Permanent Teeth: A Randomized Control Study

Objective: To compare the level of pain relief that two NSAID salts offer following a simple closed tooth extraction technique, as well as to assess patient adherence to the prescribed dosage schedule. Methodology: This Randomized Control Design study was conducted at Islamabad medical &amp; dental college, from 2018-2019. 150 patients made up the sample, who were split into two equal groups using a computerized lottery system: the experimental group and the control group. Following tooth extraction under local anesthesia, participants in the experimental group were told to take one 200 mg tablet of celecoxib orally for two days, while the control group was administered two 550 mg tablets of Naproxen Sodium orally twice a day. The standard Visual Analogue Scale (VAS) was used to assess post-extraction pain after 24 and 48 hours. Patients' adherence was verified by having them fill out a Performa form by phone call after 48 hours. After collection of Data, analysis was done with the help of SPSS version 21.0. Results: After tooth extraction, both medications were similarly effective in reducing pain, although participants adhered to the OD dose of celecoxib substantially more than the BD dose of naproxen sodium. Conclusion: There was statistically insignificant difference in pain relief provided by Celecoxib and Naproxen Sodium after 24 and 48 hours of single tooth extraction.

NSAIDs do not influence exercise effects on muscle size in rats or muscle protein synthesis signaling in humans

BACKGROUND: The aim of this project was to determine the impact of non-steroidal anti-inflammatory drugs (NSAIDs) on skeletal muscle adaptations to exercise. NSAIDs possess analgesic and anti‐inflammatory properties that occur by blocking cyclooxygenase (COX) enzymes, thereby inhibiting the production of prostaglandins. In the first study, we determined if low-dose chronic NSAID use affects muscle size in rodents exercising for six weeks. In the second study, we determined if a single high dose of NSAIDs effects the muscle protein synthetic signaling response to a bout of plyometric exercise. Our hypotheses were that NSAIDs would reduce both muscle size and muscle protein synthesis (MPS) signaling. METHODS: Study 1: 9-wk-old male Wistar rats (n=80) were randomized to placebo (PLA), naproxen (NAP), ibuprofen (IBU), or flurbiprofen (FLU) with or without exercise (EX) for six weeks. Exercise consisted of treadmill running at 25 m/min, for 30 minutes per day, five days per week. Soleus muscle was stained for myosin heavy chain (MHC) I or MHC IIA then analyzed for cross sectional area (CSA) and fiber type percentage. Rodent data were analyzed using a one-way ANOVA. Study 2: In a randomized, counter-balanced order, 12 participants (2 females, 10 males), performed four independent plyometric exercise bouts consisting of 10 sets of 10 plyometric jumps at 40% of their 1RM, separated by a minimum of one week. Prior to each session, participants consumed a single dose of celecoxib (CEL 200 mg), IBU (800 mg), FLU (100 mg) or PLA. Muscle biopsies were collected before (PRE) and 3-hours post (POST) exercise. Muscle was analyzed via immunoblot for the following: phospho(p)-AKT(S473), total AKT, p-mTOR (S448), total mTOR, p-S6 (S235/236), total S6, p-4EBP1, and total 4EBP1. Fold changes were calculated from PRE to POST. Data were analyzed using a repeated measures ANOVA. All data are presented as mean ± SD. RESULTS: Study 1: There was no significant difference (p&lt;0.05) in muscle CSA (PLA: 4060±517; PLA+EX: 3965±605; IBU: 3720±804; IBU+EX:4129±477; FLU: 3743±671; FLU+EX: 3649±541; NAP: 4157±1011; NAP+EX: 4123±586) or MHC IIA percentage (PLA: 10±7; PLA+EX: 10±5; IBU: 7±5; IBU+EX:9±3; FLU: 11±4; FLU+EX: 11±6; NAP: 11±4; NAP+EX: 12±3) between groups. Study 2: There was no significant difference (p&lt;0.05) in fold-change between groups for p-AKT/total AKT (PLA: 1.23±0.4; IBU: 1.13±0.3; CEL: 1.26±0.4; FLU: 1.31±0.4), p-mTOR/total mTOR (PLA: 1.21±0.2; IBU: 1.21±0.3; CEL:1.34±0.2; FLU: 1.49±0.3), p-S6/total S6 (PLA: 11.48±10.6; IBU: 10.9±6.8; CEL: 6.01±2.98; FLU: 25.25±19.38), or p-4EBP1/total 4EBP1 (PLA: 1.71± 1.35; IBU: 1.23±0.98; CEL: 1.07 ±0.64; FLU: 2.03±1.49). CONCLUSION: Chronic low-dose NSAID consumption does not influence muscle size or MHC in exercising rodents. Similarly, an acute high dose of an NSAID does not affect the MPS signaling response in exercising humans. Funding was provided by the Military Operational Medicine Research Program. The opinions or assertions contained herein are the private views of the author(s) and are not to be construed as offcial or as reflecting the views of the Army or the Department of Defense. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Celecoxib abrogates concanavalin A-induced hepatitis in mice: Possible involvement of Nrf2/HO-1, JNK signaling pathways and COX-2 expression.

Concanavalin A (ConA) is an established model for inducing autoimmune hepatitis (AIH) in mice, mimicking clinical features in human. The aimof the current study is to explore the possible protective effect of celecoxib, a cyclooxygenase-2 inhibitor,on immunological responses elicited in the ConA model of acute hepatitis. ConA (20mg/kg) was administered intravenously to adult male mice for 6h. Prior to ConA intoxication, mice in the treatedgroups received daily doses of celecoxib (30 and 60mg/kg in CMC) for 7days. Results revealed that administration of celecoxib 60mg/kg for 7days significantly protected the liver from ConA-induced liver damage revealed by significant decrease in ALT and AST serum levels. Celecoxib 30 and 60mg/kg pretreatment enhanced oxidant/antioxidant hemostasis by significantreduction of MDA and NO content and increase hepatic GSH contents and SOD activity. In addition, celecoxib 30 and 60mg/kg caused significant increase in hepatic nuclear factor erythroid 2-related factor 2 (Nrf2) and the stress protein heme oxygenase-1 (HO-1) levels. Moreover, celecoxib 30 and 60mg/kg inhibited the release of proinflammatory markers including IL-1β and TNF-α along with significant decrease in p-JNK, AKT phosphorylation ratio and caspase-3 expression. Besides, Con A was correlated to high expression of cyclooxygenase COX-2 and this increasing was improved by administration of celecoxib. These changes were in good agreement with improvement in histological deterioration. The protective effect of celecoxib was also associated with significant reduction of autophagy biomarkers (Beclin-1 and LC3II). In conclusion, celecoxib showed antioxidant, anti-inflammatory, anti-apoptotic and anti-autophagy activity against Con A-induced immune-mediated hepatitis. These effects could be produced by modulation of Nrf2/HO-1, IL-1B /p-JNK/p-AKT, JNK/caspase-3, and Beclin-1/LC3II signaling pathways.

Investigations of Lipid Droplets Role in Attenuating Chemotherapeutic Responses to 5-FU in Cancer Cells in vitro

Cancer has been considered as a main cause of death worldwide. Despite the effectiveness of traditional anticancer therapies such as 5-Flurouracil (5-FU), poor therapeutic outcomes are reported in many cases, due to tumor recurrence and chemoresistance. Intracellular lipid accumulation as lipid droplets (LDs) is now a well-recognized hallmark of cancer. However, the influence of LDs accumulation in cancer progression and treatment remains to be elucidated. Adjuvant use of non-chemotherapeutic drugs (e.g. NSAIDs and corticosteroids) with anticancer drugs to manage cancer related symptoms, may though serve as factors modulating the therapeutic response to anticancer agents via LDs related mechanisms. The aim of this study is to evaluate possible strategies influencing chemoresistance by attenuating LDs biogenesis and function. LDs levels in eight human cancer cell lines were measured. The existence of correlation between the cellular levels of LDs and cytotoxicity of ten chemotherapeutic agents was evaluated. A moderate correlation between basal LDs levels and the half inhibitory concentration (IC50) values of 5-FU on selected cell lines was established (r2= 0.5235). Nevertheless, LDs levels were significantly elevated following exposure to 5-FU. A549 human lung cancer cells showed the highest increase in LD accumulation (***P &gt;0.001) compared to their basal levels of LDs. LDs levels were also assessed following exposure to 5-FU in the presence of sub-lethal doses of celecoxib (CXB), dexamethasone (DEX), and simvastatin (SMV). Interestingly, CXB and DEX exposure to 5-FUtreated cells resulted in an alleviation in the antiproliferative activities of 5-FU in MDA-MB-468 and HCT116 but not in A549 cells. While, SMV exposure to 5-FU-treated cells resulted in reduced antiproliferative activities of 5-FU in MDA-MB-468 only. These results strongly suggest that increased LDs levels caused by CXB, DEX, and SMV may contribute in the development of a resistance mechanism exist only in some cancer types, which therefore, attenuates responses to 5- FU. The inhibition of phospholipid metabolism by DEX, as well as the inhibition of 3-hydroxy-3- methylglutaryl-CoA reductase (HMGCR) by SMV were expected to result in the up regulation of triacylglycerol (TAG), leading to LDs accumulation. This study highlights the importance of assessing drug-drug interaction before designing integrated therapy regimens for cancer patients receiving 5-FU treatment. Further studies are needed to discover the role of TAG inhibition on the sensitivity of cancer cells against 5-FU.

Celecoxib Oral Solution and the Benefits of Self-Microemulsifying Drug Delivery Systems (SMEDDS) Technology: A Narrative Review.

The oral route of drug delivery is the most widespread and preferred route of administration, but it has several limitations, including variable pharmacokinetics (PK), reduced dissolution and absorption, and gastrointestinal irritation. Further, many compounds have low aqueous solubility, which also limits intestinal absorption. For this narrative review, we conducted a literature search of PubMed until August 2022, focusing on emulsions, microemulsions, nanoemulsions, and self-emulsifying drug delivery systems. The self-microemulsifying drug delivery system (SMEDDS) overcomes these limitations of hydrophobic compounds to enhance their bioavailability. A SMEDDS formulation is a clear, thermodynamically stable, oil-in-water emulsion of lipid, solubilized drug, and two surfactants, which spontaneously forms droplets < 100nm in diameter. These components help deliver presolubilized drugs to the gastrointestinal tract, while protecting them from degradation in gastric acid or first-pass hepatic metabolism. SMEDDS formulations have improved oral drug delivery in the treatment of cancer (paclitaxel), viral infections (ritonavir), and migraine headache (ibuprofen and celecoxib oral solution). The American Headache Society recently updated their consensus statement for the acute treatment of migraine and included a selective cyclo-oxygenase-2 selective inhibitor formulated in SMEDDS, celecoxib oral solution. This SMEDDS formulation showed pronounced improvement in bioavailability compared with celecoxib capsules, allowing for a low dose of celecoxib in the oral solution to provide safe and effective acute migraine treatment. Here, we will focus on SMEDDS formulations, what differentiates them from other analogous emulsions as vehicles for poorly soluble drugs, and their clinical application in the acute treatment of migraine. Oral drugs reformulated in SMEDDS have shown accelerated times to peak plasma drug concentrations and increased maximum plasma concentrations, compared with capsules, tablets, or suspensions. SMEDDS technology increases both drug absorption and bioavailability of lipophilic drugs, compared with other formulations. Clinically, this allows the use of lower doses with improved PK profiles without compromising efficacy, as shown with celecoxib oral solution for the acute treatment of migraine.

A Short Course of Celecoxib Prevents Heterotopic Ossification Following Cementless Total Hip Arthroplasty.

Heterotopic ossification (HO) is a common complication after total hip arthroplasty (THA) and can result in pain and loss of motion of the hip. This is the first study in the literature to determine if a short course of Celecoxib is effective in the prevention of HO in patients undergoing cementless THA. In this retrospective study of prospectively collected data, consecutive patients undergoing a primary cementless THA were reviewed at a 2-year follow-up. The Control group consisted of 104 hips that did not receive Celecoxib (Control group), while the 208 hips in the Celecoxib group received 100 mg twice daily for 10 days. Radiographs, patient-recorded outcome measures and range of motion (ROM) were evaluated. Overall, there was a significantly decreased incidence of HO in the Celecoxib group (18.7%) than in the Control group (31.7%) (p = 0.01). The odds that a patient developed HO using Celecoxib were 0.4965 times the odds that a patient developed HO without treatment. Clinically, the Celecoxib group demonstrated significantly greater improvement in their mean WOMAC stiffness (0.35 vs. 0.17, p = 0.02) and physical function scores (3.26 vs. 1.83, p = 0.03) compared to those in the Control group, but there was no difference in the ROM between the two groups. This study is the first to demonstrate that the lowest dose of Celecoxib for a short course of only 10 days is a simple and effective prophylactic treatment option that can significantly reduce the incidence of HO following cementless THA.

Phase I Study of a Combination of Fluvastatin and Celecoxib in Children with Relapsing/Refractory Low-Grade or High-Grade Glioma (FLUVABREX)

Preclinical data support the activity of celecoxib and fluvastatin in high-grade (HGG) and low-grade gliomas (LGG). A phase I trial (NCT02115074) was designed to evaluate the safety of this combination in children with refractory/relapsed HGG and LGG using four dose levels of fluvastatin with a fixed daily dose of celecoxib. A Continual Reassessment Method was used for fluvastatin dose escalation. Dose-limiting toxicities (DLT) were determined on the first treatment cycle. Twenty patients were included. Ten LGG and ten HGG patients received a median of 3.5 treatment cycles. Two DLTs were reported: one grade 3 maculopapular rash (4 mg/kg dose level) and one grade 4 increase of Creatine Phospho-Kinase (6 mg/kg dose level). We identified the dose of 6 mg/kg/day as the recommended phase II dose (RP2D) of fluvastatin with celecoxib. Four patients with LGG continued treatment beyond 12 cycles because of stable disease, including one patient who received 23 treatment cycles. In children with refractory/relapsed glioma, the RP2D of fluvastatin with celecoxib is 6 mg/kg/day. The long-term stable diseases observed in LGG suggest a possible role of the combination in a maintenance setting, given its good tolerance and low cost for children living in low- and middle-income countries.

Does etodolac affect TRPA1 functionality invivo in human?

In preclinical research, etodolac, a non-steroidal anti-inflammatory drug, affected transient receptor potential ankyrin 1 (TRPA1) activation. Yet, whether the invitro interaction between etodolac and TRPA1 translates to altered TRPA1 functionality invivo in human remains to be investigated. A randomized, double-blinded, celecoxib-controlled study was conducted to assess the effect of etodolac on TRPA1-mediated dermal blood flow (DBF) changes on the forearm of 15 healthy, male volunteers aged between 18 and 45 years. Over four study visits, separated by at least five days wash-out, a single or four-fold dose of etodolac 200mg or celecoxib 200mg was administered orally. Two hours post-dose, TRPA1 functionality was evaluated by assessing cinnamaldehyde-induced DBF changes. DBF changes were quantified and expressed in Perfusion Units(PUs) using laser Doppler imaging during 60min post-cinnamaldehyde application. The corresponding area under the curve (AUC0-60min) was calculated as summary measure. Statistical analysis was performed using Linear mixed models with post-hoc Dunnett. Neither the single dose of etodolac nor celecoxib inhibited the cinnamaldehyde-induced DBF changes compared to no treatment (AUC0-60min±SEM of 17,751±1,514 PUs*min and 17,532±1,706 PUs*min vs. 19,274±1,031 PUs*min, respectively, both p=1.00). Similarly, also a four-fold dose of both compounds failed to inhibit the cinnamaldehyde-induced DBF changes (19,235±1,260 PUs*min and 19,367±1,085 PUs*min vs. 19,274±1,031 PUs*min, respectively, both p=1.00). Etodolac did not affect the cinnamaldehyde-induced DBF changes, suggesting that it does not alter TRPA1 functionality invivo in human.

Efficacy and safety of the ghrelin-O-acyltransferase inhibitor BI 1356225 in overweight/obesity: Data from two Phase I, randomised, placebo-controlled studies

BackgroundObesity is a complex disease associated with multiple concurrent complications, and the coordinated targeting of multiple pathways in pharmacological treatment may improve weight loss outcomes. During synthesis, ghrelin is converted from the ‘inactive’ unacylated ghrelin (UAG) to the active acylated ghrelin (AG) by the enzyme ghrelin-O-acyltransferase (GOAT), stimulating appetite and food intake. AimsTo report the results of two Phase I studies investigating single rising doses (SRDs) or multiple rising doses (MRDs) of the novel oral GOAT inhibitor BI 1356225 versus placebo in male and postmenopausal/sterilised female subjects with overweight or obesity. MethodsThe SRD study investigated single doses of BI 1356225 (0.1–20.0 mg) in healthy male subjects with a BMI of 18.5–29.9 kg/m2 (SRD cohort) and assessed doses of 2.5 mg BI 1356225 under fed and fasted conditions (bioavailability [BA] cohort). The MRD study investigated multiple doses of BI 1356225 (0.2, 1.0, 2.5 or 10.0 mg) or 5.0 mg BI 1356225 with a single dose of midazolam and celecoxib (drug–drug interaction part) over 28 days in adults with a BMI of 27.0–39.9 kg/m2. ResultsSixty-five subjects were treated in the SRD study. Drug-related adverse events (AEs) were reported for five subjects (9.1 %) in the SRD cohort and two subjects (20.0 %) in the BA cohort, with the most frequent being headache (SRD: n = 4, 9.8 %; BA: n = 1, 10.0 %). In the MRD study, two (2.3 %) of the 87 subjects treated discontinued treatment because of AEs. Drug-related AEs were reported for 18 subjects (20.7 %), did not increase with dose and were most frequently reported as headache (n = 5, 5.7 %) and gastrointestinal disorders (n = 5, 5.7 %). In both studies, exposure parameters (area under the concentration–time curve [AUC] and maximum plasma concentration [Cmax]) of BI 1356225 increased across dose groups, although this was less than dose-proportional across the entire dose range. In the BA cohort of the SRD study, AUC0–∞ was slightly increased and Cmax slightly decreased in fed versus fasted conditions, with fed/fasted ratios (90 % CI) of 101.10 % (92.42, 110.60) and 91.67 % (78.50, 107.05), respectively. In both studies, AG concentrations and the AG/UAG ratio were dose-dependently decreased after BI 1356225 treatment from baseline versus placebo. In the MRD study, UAG concentrations were increased from baseline, but not dose-dependently. No differences were observed in bodyweight, appetite, food cravings, ad libitum food uptake or obesity-related biomarkers after 28 days of treatment with BI 1356225. ConclusionsTreatment with SRDs and MRDs of BI 1356225 was well tolerated by healthy males and subjects with overweight/obesity. BI 1356225 treatment over 28 days reduced AG concentrations and the AG/UAG ratio by >80 %, but no effect was seen on bodyweight, hunger/satiety, control of eating or energy intake. Although, at 4 weeks, the MRD study was fairly short, a reduction in bodyweight would be expected to be evident by this time, suggesting that a reduction of AG via a GOAT inhibitor is not sufficient to induce clinically relevant bodyweight loss.

Scheduled, Simultaneous Dosing of Pregabalin, Celecoxib, and Acetaminophen Markedly Reduces or Eliminates Opioid Use After ACL Reconstruction Using Allograft or Hamstring Tendon Autograft: A Randomized Clinical Trial

Opioid analgesics continue to be prescribed after ambulatory surgery despite untoward adverse effects, risk of overdose, and association with substance use disorder. The purpose was to investigate the use of a novel system to provide scheduled and simultaneous dosing of acetaminophen, celecoxib, and pregabalin after anterior cruciate ligament reconstruction (ACLR). It was hypothesized that this system would markedly reduce pain and opioid use compared with existing best practice. Randomized controlled trial; Level of evidence, 1. Included were 100 patients scheduled for elective, primary ACLR using allograft or hamstring tendon autograft. Selection criteria included age between 18 and 65 years and weight between 65 and 120 kg. Exclusion criteria were a known allergy to any drug used in the study or the use of opioid analgesics before surgery. Patients in the intervention group received a blister pack with scheduled, simultaneous doses of acetaminophen, celecoxib, and pregabalin; patients were also given oxycodone 5 mg as needed for breakthrough pain. Patients in the control group were prescribed ibuprofen and oxycodone 5 mg/acetaminophen 325 mg as needed for pain. The primary outcome measure was pain. Secondary outcomes were nausea, itching, and daily oxycodone use. Patients were asked to quantify their average pain at rest, nausea, and itching on an 11-point verbal scale (from 0 to 10). These data were recorded for 6 days during daily telephone contacts with patients after hospital discharge. Cumulative results for 6 days showed significantly lower values in the intervention group compared with the control group for pain (median [interquartile range], 28 [14-35] vs 35 [28-41], respectively; P = .009) and oxycodone use (median [interquartile range] number of tablets, 0 [0-2] vs 8 [1.25-16], respectively; P < .001). Based on these data, the upper tolerance limits for the number of oxycodone tablets required by 90% of patients in the intervention and control groups were 8 tablets and 30 tablets, respectively. Cumulative results for nausea and itching were also significantly lower for the intervention group. Most patients in the intervention group used no opioids during recovery. Simultaneous dosing of 3 nonopioid analgesics resulted in reduced postoperative pain and markedly lower opioid use. NCT04015908 (ClinicalTrials.gov identifier).

Low Doses of Celecoxib Might Promote Phenotype Switching in Cutaneous Melanoma Treated with Dabrafenib-Preliminary Study.

Background: Cutaneous melanoma is a heterogeneous tumor with a rapidly switching molecular and cellular phenotype. The invasive phenotype switching characterized by MITFlow/AXLhigh predicts early resistance to multiple targeted drugs in melanoma. Celecoxib proved to be a valuable adjuvant in cutaneous melanoma in preclinical studies. Our in vitro study evaluated for the first time whether celecoxib could prevent phenotype switching in two human melanoma cell lines treated with dabrafenib. Methods: All in vitro experiments were carried out on BRAF-V600E-positive A375 and SK-MEL-28 human melanoma cell lines, and subjected to a celecoxib and dabrafenib drug combination for 72 h. Melanoma cells were already in the MITFlow/AXLhigh end of the spectrum. Of main interest was the evaluation of the key proteins expressed in phenotype switching (TGF-β, MITF, AXL, YAP, TAZ), as well as cell death mechanisms correlated with oxidative stress production. Results: Celecoxib significantly enhanced the apoptotic effect of dabrafenib in each melanoma cell line compared to the dabrafenib group (p < 0.0001). Even though celecoxib promoted low MITF expression, this was correlated with high receptor tyrosine kinase AXL levels in A375 and SK-MEL-28 cell lines (p < 0.0001), a positive marker for the phenotype switch to an invasive state. Conclusion: This preliminary study highlighted that celecoxib might promote MITFlow/AXLhigh expression in cutaneous melanoma treated with dabrafenib, facilitating phenotype switching in vitro. Our results need further confirmation, as this finding could represent an important limitation of celecoxib as an antineoplastic drug.

Short-term celecoxib (celebrex) adjuvant therapy: a clinical trial study on COVID-19 patients.

BackgroundIt is known that severe acute respiratory coronavirus 2 (SARS-CoV-2) is the viral strain responsible for the recent coronavirus disease 2019 (COVID-19) pandemic. Current documents have demonstrated that the virus causes a PGE2 storm in a substantial proportion of patients via upregulating cyclooxygenase-2 (COX-2) and downregulating prostaglandin E2 (PGE2)-degrading enzymes within the host cell.AimHerein, we aimed to study how short-term treatment with celecoxib (Celebrex), a selective COX-2 inhibitor, affects demographic features, early symptoms, O2 saturation, and hematological indices of cases with COVID-19.MethodsA total of 67 confirmed COVID-19 cases with a mild or moderate disease, who had been referred to an institutional hospital in south-eastern Iran from October 2020 to September 2021, were enrolled. Demographic characteristics, symptoms, and hematological indices of the patients were recorded within different time periods. One-way ANOVA or Kruskal–Wallis tests were used to determine differences between data sets based on normal data distribution.ResultsO2 saturation was statistically different between the control group and patients receiving celecoxib (p = 0.039). There was no marked difference between the groups in terms of the symptoms they experienced (p > 0.05). On the first days following Celebrex therapy, analysis of complete blood counts showed that white blood cell (WBC) counts were markedly lower in patients treated with a high dose of celecoxib (0.4 g/day) than in controls (p = 0.026). However, mean lymphocyte levels in patients receiving a high dose of celecoxib (0.4 g/day) were markedly higher than in patients receiving celecoxib with half of the dose (0.2 g/day) for one week or the untreated subjects (p = 0.004). Changes in platelet count also followed the WBC alteration pattern.ConclusionCelecoxib is a relatively safe, inexpensive, and widely available drug with non-steroidal anti-inflammatory properties. The therapeutic efficacy of celecoxib depends on the administrated dose. Celecoxib might improve disease-free survival in patients with COVID-19.

Cyclic Metronomic Chemotherapy for Pediatric Tumors: Six Case Reports and a Review of the Literature.

We report a retrospective case series of six Hispanic children with tumors treated with metronomic chemotherapy. The six cases comprised one rhabdoid tumor of the kidney, one ependymoma, two medulloblastomas, one neuroblastoma, and a type II neurocytoma of the spine. Treatment included oral cyclophosphamide daily for 21 days alternating with oral etoposide daily for 21 days in a backbone of daily valproic acid and celecoxib. In one case, celecoxib was substituted with sulindac. Of the six patients, three showed complete responses, and all patients showed some response to metronomic therapy with only minor hematologic toxicity. One patient had hemorrhagic gastritis likely associated with NSAIDs while off prophylactic antacids. These data add to a growing body of evidence suggesting that continuous doses of valproic acid and celecoxib coupled with alternating metronomic chemotherapy of agents such as etoposide and cyclophosphamide can produce responses in pediatric tumors relapsing to conventional dose chemotherapy.

Selective COX-2 inhibitor continues to be a safe alternative in patients with nonselective NSAIDs hypersensitivity

Background: Nonsteroidal anti-inflammatory drugs (NSAIDs) cause different types of allergic and pseudo allergic reactions. This results in difficulties in clinical practice. Most cases of NSAID hypersensitivity are mediated by the inhibition of cyclooxygenase-1 enzyme (COX-1), which results in depletion of the protective prostaglandin E2, and promotes the unrestrained synthesis of inflammatory mediators from mast cells. Selective COX-2 inhibitors are considered safe alternatives in patients with NSAID allergy, although hypersensitivity reactions to COX-2 inhibitors have also been reported. Our study aimed to report the experience in Qatar for using COX2 inhibitors as an alternative treatment for nonselective NSAID allergy.Methods: Data of patients who underwent open challenge with a single dose of oral celecoxib 200 mg were retrieved from the procedure log of the Allergy and immunology Division in Hamad medical corporation, Doha, Qatar, from 2013 to 2022. The challenge was considered positive if the patient developed cutaneous or respiratory symptoms.Results: A total of 31 patients were identified; 4 with a history of celecoxib allergy. The remaining 27 (23 females and 4 males); with mean ( ± SD, range) age of 42 ( ± 12, 20–65) years had hypersensitivity to one (n = 11) or more than one (n = 16) nonselective NSAID, manifested as cutaneous, respiratory, or anaphylactic symptoms. Those 4 patients with celecoxib allergy were challenged and only one with a historical reaction of anaphylaxis developed anaphylaxis during the challenge. Celecoxib was well tolerated in all 27 patients with hypersensitivity reactions to nonselective NSAIDs. Also, patients were contacted by telephone call at 24 hours and after 1 week with no evidence of delayed reactions.Conclusions: Selective COX-2 and nonselective NSAIDs have similar overall efficacy as analgesic, anti-inflammatory, and antipyretic agents. Hypersensitivity reaction to COX-2 inhibitors has been reported; however, it is rare. So, it is safer to challenge the patients with COX-2 inhibitors before prescribing them as alternative medication in patients with Nonselective NSAID allergies. We plan to conduct a single-/double-blind placebo-controlled study for more patients, especially using graded challenges for high-risk profile candidates. Also, it may be of significance to test more than one type of selective COX-2 to avoid drug-specific reactions.

TiaochangXiaoliu decoction inhibits azomethane (AOM)/dextran sulfate sodium (DSS)-induced colorectal cancer by regulating immune response.

TiaochangXiaoliu decoction (TXD) has an anti-tumor effect in clinical practice. We further investigated the role of TXD in colorectal cancer (CRC). Mouse models of CRC were induced by azomethane (AOM)/dextran sulfate sodium (DSS), with sixty male C57BL/6 mice randomly divided into six groups (10 mice/group): a control group, AOM/DSS group, TXD at low dose (L-dose) group, middle dose (M-dose) group, high dose (H-dose) group, and Celecoxib (Cel) group. The colorectum, serum, and plasma of mice in each group was collected following sacrifice to record the number of tumors. HE staining was utilized for observing pathological damage to colorectal tissues, ELISA used for detecting INF-γ, IL-2, and TNF-α expression in serum, and flow cytometry used for measuring the proportion of CD4+, CD8+, CD4+/CD8+, and NK cells in plasma. Compared with the control group, the AOM/DSS group showed tumor masses in the colorectum and different degrees of pathological damage in the intestine. AOM/DSS induction also resulted in an increase in INF-γ, IL-2, and TNF-α expression in serum, and a decrease in the percentages of CD4+, CD8+, CD4+/CD8+, and NK cells(P<0.05). In comparison with the AOM/DSS group, with the increase of TXD dose, the number of tumors decreased significantly, and intestinal structure and mucosal inflammatory cell infiltration also improved. Further, in comparison with the AOM/DSS group, all three doses of TXD and celecoxib caused an increase in the contents of CD4+, CD8+, CD4+/CD8+, and NK cells in plasma. In addition, in the M-dose, H-dose, and Cel groups, INF-γ, IL-2, and TNF-α expression showed a marked decrease, and the reduction in these two groups treated with TXD was dose-dependent. TXD leads to a marked reduction in the number of tumors and inflammatory cell infiltration in CRC mice. This decoction significantly decreased the levels of INF-γ, IL-2, and TNF-α in serum, and increased the contents of CD4+, CD8+, CD4+/CD8+, and NK cell in the plasma of mice with AOM/DSS-induced CRC.

Effect of Celecoxib vs Placebo as Adjuvant Therapy on Disease-Free Survival Among Patients With Breast Cancer

Patients with breast cancer remain at risk of relapse after adjuvant therapy. Celecoxib has shown antitumor effects in preclinical models of human breast cancer, but clinical evidence is lacking. To evaluate the role of celecoxib as an addition to conventional therapy for women with ERBB2 (formerly HER2)-negative primary breast cancer. The Randomized European Celecoxib Trial (REACT) was a phase 3, randomized, double-blind study conducted in 160 centers across the UK and Germany testing 2 years of adjuvant celecoxib vs placebo among 2639 patients recruited between January 19, 2007, and November 1, 2012, with follow-up 10 years after treatment completion. Eligible patients had completely resected breast cancer with local and systemic therapy according to local practice. Patients with ERBB2-positive or node-negative and T1, grade 1 tumors were not eligible. Randomization was in a 2:1 ratio between celecoxib or placebo. Statistical analysis was performed from May 5, 2019, to March 5, 2020. Patients received celecoxib, 400 mg, or placebo once daily for 2 years. The primary end point was disease-free survival (DFS), analyzed in the intention-to-treat population using Cox proportional hazards regression and log-rank analysis. Follow-up is complete. A total of 2639 patients (median age, 55.2 years [range, 26.8-86.0 years]) were recruited; 1763 received celecoxib, and 876 received placebo. Most patients' tumors (1930 [73%]) were estrogen receptor positive or progesterone receptor positive and ERBB2 negative. A total of 1265 patients (48%) had node-positive disease, and 1111 (42%) had grade 3 tumors. At a median follow-up of 74.3 months (interquartile range, 61.4-93.6 years), DFS events had been reported for 487 patients (19%): 18% for those who received celecoxib (n = 323; 5-year DFS rate = 84%) vs 19% for those who received placebo (n = 164; 5-year DFS rate = 83%); the unadjusted hazard ratio was 0.97 (95% CI, 0.80-1.17; log-rank P = .75). Rates of toxic effects were low across both treatment groups, with no evidence of a difference. In this randomized clinical trial, patients showed no evidence of a DFS benefit for 2 years' treatment with celecoxib compared with placebo as adjuvant treatment of ERBB2-negative breast cancer. Longer-term treatment or use of a higher dose of celecoxib may lead to a DFS benefit, but further studies would be required to test this possibility. ClinicalTrials.gov Identifier: NCT02429427 and isrctn.org Identifier: ISRCTN48254013.

Comparison of Postoperative Pain Management Post Third Molar Surgery with Low Pre-Emptive Oral Doses of Celecoxib versus Acetaminophen: A Randomized Controlled Trial (RCT)

Comparison of Postoperative Pain Management Post Third Molar Surgery with Low Pre-Emptive Oral Doses of Celecoxib versus Acetaminophen: A Randomized Controlled Trial (RCT)

Low-dose cyclooxygenase-2 (COX-2) inhibitor celecoxib plays a protective role in the rat model of neonatal necrotizing enterocolitis

ABSTRACT This study aims to investigate the effects of the cyclooxygenase-2 (COX-2) inhibitor celecoxib on neonatal necrotizing enterocolitis (NEC) in rats. After treatment with a low dose of celecoxib (0.5, 1, or 1.5 mg/kg), pathological changes in the ileum and the levels of oxidative stress and inflammatory factors in NEC rats were compared. Enzyme-linked immunosorbent assay (ELISA) was employed to detect inflammatory factors, terminal deoxyribonucleotidyl transferase (TdT)-mediated biotin-16-dUTP nick-end labeling (TUNEL) staining was employed to assess apoptotic epithelial cells in the ileum, and real-time quantitative polymerase chain reaction (qRT-PCR) and Western blotting were used to quantify gene and protein expression, respectively. The incidences of NEC rats in the 0.5, 1 and 1.5 mg/kg celecoxib groups were lower than in the model group (100%). Celecoxib improved the histopathology of the ileum in NEC rats. Moreover, low doses of celecoxib relieved oxidative stress and inflammation in NEC rats, as evidenced by decreased tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), total oxidation state (TOS), malondialdehyde (MDA) and oxidative stress index (OSI), as well as increased interleukin-10 (IL-10), total antioxidant status (TAS), superoxide dismutase (SOD) and glutathione peroxidase (GPx). With increasing celecoxib doses (0.5, 1, or 1.5 mg/kg), the amount of apoptotic epithelial cells in the ileum of NEC rats gradually declined and Caspase-3 expression was reduced. The low dose of the COX-2 inhibitor celecoxib ameliorated the histopathologic conditions of the ileum, alleviated oxidative stress and inflammation, and reduced apoptotic epithelial cells in NEC rats, thereby making it a potential therapy for NEC.