Effect of Oxycodone-Based Multimodal Analgesia on Visceral Pain After Major Laparoscopic Gastrointestinal Surgery: A Randomised, Double-Blind, Controlled Trial.

Purpose: Oxycodone is a potent µ- and κ-opioid receptor agonist that can relieve both somatic and visceral pain. We assessed oxycodone- vs sufentanil-based multimodal analgesia on postoperative pain following major laparoscopic gastrointestinal surgery. Methods: In this randomised double-blind controlled trial, 40 adult patients were randomised (1:1, stratified by type of surgery) to receive oxycodone- or sufentanil-based multimodal analgesia, comprising bilateral transverse abdominis plane blocks, intraoperative dexmedetomidine infusion, flurbiprofen axetil, and oxycodone- or sufentanil-based patient-controlled analgesia. The co-primary outcomes were time-weighted average (TWA) of visceral pain (defined as intra-abdominal deep and dull pain) at rest and on coughing during 0-24 h postoperatively, assessed using the numerical rating scale (0-10) with a minimal clinically important difference of 1. Results: All patients completed the study (median age, 64 years; 65% male) and had adequate postoperative pain control. The mean (SD) 24-h TWA of visceral pain at rest was 1.40 (0.77) in the oxycodone group vs 2.00 (0.98) in the sufentanil group (mean difference=-0.60, 95% CI, -1.16 to -0.03; P=0.039). Patients in the oxycodone group had a significantly lower 24-h TWA of visceral pain on coughing (2.00 [0.83] vs 2.98 [1.26]; mean difference=-0.98, 95% CI, -1.66 to -0.30; P=0.006). In the subgroup analyses, the treatment effect of oxycodone vs sufentanil on the co-primary outcomes did not differ in terms of age (18-65 years or >65 years), sex (female or male), or type of surgery (colorectal or gastric). Secondary outcomes (24-h TWA of incisional and shoulder pain, postoperative analgesic usage, rescue analgesia, adverse events, and patient satisfaction) were comparable between groups. Conclusion: For patients undergoing major laparoscopic gastrointestinal surgery, oxycodone-based multimodal analgesia reduced postoperative visceral pain in a statistically significant but not clinically important manner. Trial Registration: Chinese Clinical Trial Registry (ChiCTR2100052085).

Evaluation of the Clinical Drug-Drug Interaction Potential of Pritelivir on Transporters and CYP450 Enzymes Using a Cocktail Approach.

Pritelivir is a novel viral helicase-primase inhibitor active against herpes simplex virus. In vitro drug-drug interaction studies indicated that pritelivir has the potential for clinically relevant interactions on the cytochrome P450 (CYP) enzymes 2C8, 2C9, 3A4, and 2B6, and intestinal uptake transporter organic anion transporting polypeptide (OATP) 2B1 and efflux transporter breast cancer resistance protein (BCRP). This was evaluated in 2 clinical trials. In 1 trial the substrates flurbiprofen (CYP2C9), bupropion (CYP2B6), and midazolam (CYP3A4) were administered simultaneously as part of the Geneva cocktail, while the substrate celiprolol (OAPT2B1) was administered separately. In another trial, the substrates repaglinide (CYP2C8) and rosuvastatin (BCRP) were administered separately. Exposure parameters of the substrates and their metabolites (flurbiprofen and bupropion only) were compared after administration with or without pritelivir under therapeutic concentrations. The results of these trials indicated that pritelivir has no clinically relevant effect on the exposure of substrates for the intestinal uptake transporter OATP2B1 and the CYP enzymes 3A4, 2B6, 2C9, and 2C8, and has a weak inhibitory effect on the intestinal efflux transporter BCRP. In summary, the results suggest that pritelivir has a low drug-drug interaction potential.

Flurbiprofen in the subglottic space to prevent postoperative sore throat after cardiac surgery: A randomized double-blind study.

STUDY OBJECTIVE: Postoperative sore throat (POST) and hoarseness are common complications of tracheal intubation. This study aims to evaluate the efficacy of flurbiprofen administered through the subglottic port of tracheal tubes to prevent POST after cardiac surgery. DESIGN: Single-center, prospective, randomized, double-blind, placebo-controlled trial. SETTING: Tertiary Care Referral University Hospital (Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome). PATIENTS: Included 71 patients undergoing for elective cardiac surgery. Inclusion criteria were (a) age between 50 and 75 years, (b) NYHA class I or II, (c) surgery for myocardial revascularization or valve repair or replacement under cardiopulmonary bypass. INTERVENTION: Patients were double blind randomized to receive flurbiprofen or saline in the subglottic port of the endotracheal tube (groups F and P). The solution was injected ten minutes after tracheal tube placement, ten minutes after ICU admission and ten minutes before tracheal tube removal. MEASUREMENTS: The primary outcome was to assess the effect of topical flurbiprofen administered through the subglottic port of the tracheal tube to prevent post-operative sore throat (POST). The secondary outcomes were the presence of hoarseness safety and patient's subjective satisfaction with their recovery. We did not report any exploratory outcomes. MAIN RESULTS: We analyzed 68 patients, 34 patients in each group. In group F, two patients complained of POST and hoarseness (5.9%), while all controls did. The two groups significantly differed in the severity scores (VAS and TPS for sore throat and HOAR for hoarseness) at all time points. In group P, patients reported mild to moderate symptoms that significantly improved or disappeared 36 h after tracheal tube removal. According to the multivariable model, hoarseness affected women less than men, in the control group (p = 0.002). None of the patients in either group reported any adverse effects. CONCLUSIONS: Repeated administration of flurbiprofen through the subglottic port of tracheal tubes reduced the incidence of sore throat and hoarseness after cardiac surgery without evidence of complications.

Defining the Conformational Ensembles Associated with Ligand Binding to Cyclooxygenase-2.

Cyclooxygenases (COX) catalyze the committed step in the production of prostaglandins responsible for the maintenance of physiological homeostasis. While crystal structures of COX in complex with substrates and inhibitors have provided insight into the molecular interactions governing their binding, they have not uncovered specific details related to the protein conformational motions responsible for important aspects of the COX function. We created a cysteine-free COX-2 construct and introduced a free cysteine at position-122 to enable labeling with 3-bromo-1,1,1-trifluoroacetone (BTFA). Placement of the label adjacent to the cyclooxygenase channel entrance permitted the detection of alterations upon ligand binding. 19F-nuclear magnetic resonance spectroscopy (19F-NMR) was then used to probe the conformational ensembles arising from BTFA-labeled COX-2 constructs in the presence and absence of ligands known to allosterically activate or inhibit COX-2. 19F-NMR analyses performed in the presence of the time-dependent inhibitor flurbiprofen, as well as Arg-120, Tyr-355, and Glu-524 mutations, led to the classification of two ensembles as representing the relaxed and tightened states of the cyclooxygenase channel entrance. A third ensemble, generated in the presence of arachidonic acid and the Y355F mutant and modulated by the allosteric potentiators palmitic acid and oleic acid and the nonallosteric substrates 2-arachidonoyl glycerol ether and anandamide, was classified as being related to the allosteric regulation of COX activity. The ensemble-based insight into COX function demonstrated here complements the static information derived from crystal structure analyses, collectively providing a more detailed framework of the dynamics involved in the regulation of COX catalysis and inhibition.

Synthesis of flurbiprofen thiadiazole urea derivatives and assessment of biological activities and molecular docking studies.

Totally 15 novel flurbiprofen urea derivatives were synthesized bearing the thiadiazole ring. Their inhibition effects on tyrosinase were determined. 3c was found to be the strongest inhibitor with the IC50 value of 68.0 µM against tyrosinase. The enzyme inhibition types of the synthesized compounds were determined by examining the kinetic parameters. The inhibition type of 3c was determined as uncompetitive and the Ki value was calculated as 36.3 µM. Moreover, their cytotoxic effects on hepatocellular carcinoma (HepG2), colorectal carcinoma (HT-29), and melanoma (B16F10) cell lines were evaluated. According to the cytotoxicity results, 3l (IC50 = 14.11 µM) showed the highest cytotoxicity on the HT-29 cells, while 3o (IC50 = 4.22 µM) exhibited the strongest cytotoxic effect on HepG2 cell lines. Also, 3j (IC50 = 7.55 µM strongly affected B16F10. The effects of synthesized compounds on the healthy cell line were evaluated on the CCD-986Sk cell line. Molecular modelling studies have indicated the potential binding interactions of the uncompetitive inhibitor 3c with the enzyme-substrate complex.

Contribution of prophylactic administration of flurbiprofen for mesenteric traction syndrome to postoperative leakage or bleeding in gastrointestinal surgery: a retrospective observational study.

PURPOSE: Mesenteric traction syndrome (MTS) sometimes occurs during abdominal surgery. Prophylactic administration of flurbiprofen, a non-steroidal anti-inflammatory drug, prevents the development of MTS. However, administration of non-steroidal anti-inflammatory drugs for postoperative pain increases the incidence of postoperative bleeding. Our aim was to examine the effect of prophylactic flurbiprofen administration on postoperative leakage or bleeding after gastrointestinal surgery. METHODS: A retrospective observational study on patients who underwent open or laparoscopic abdominal surgery was conducted. Perioperative, anesthesia and medical records were reviewed. Patients who did (Flurbio-Group) or did not receive (Control-Group) prophylactic flurbiprofen administration were compared. Then, the Flurbio-Group and Control-Group were each divided into two groups according to whether the patients did or did not develop MTS (Flurbio-MTS-Group and Flurbio-no-MTS-Group, respectively, Control-MTS-Group and Control-no-MTS-Group, respectively). RESULTS: This study included 188 patients (Flurbio-MTS-Group, 1 patient; Flurbio-no-MTS-Group, 31 patients; Control-MTS-Group, 59 patients; Control-no-MTS-Group, 97 patients). Seventeen patients developed postoperative leakage or bleeding. Eleven Flurbio-MTS-Group patients (18.6%), 4 Flurbio-no-MTS-Group patients (12.9%, 4/31), and only 2 Control-no-MTS-Group patients (2%, 2/97) developed postoperative leakage or bleeding. Multivariate logistic regression analysis demonstrated that there was a qualitative interaction effect between prophylactic administration of flurbiprofen and the development of MTS on postoperative leakage or bleeding. CONCLUSION: Prophylactic flurbiprofen administration increased the risk of postoperative leakage or bleeding among patients who did not develop MTS.

Efficacy of ultrasound guided superior laryngeal nerve block on sedation for delayed extubation in maxillofacial surgery with free flap reconstruction.

OBJECTIVE: Superior laryngeal nerve block (SLNB) is a regional anesthesia technique for addressing airway response. However, SLNB on the efficacy of sedation in patients with delayed extubation is unknown, particularly for maxillofacial surgery (MS). The aim of the study was to assess whether ultrasound guided (UG) SLNB reduces the incidence of moderate to severe cough for delayed extubation in MS with free flap reconstruction. METHODS: 60 patients were randomly assigned to the GEA group (control group) and the SLNB group (UG-SLNB postoperatively, study group). During the initial two postoperative hours, the incidence of moderate and severe cough, agitation, and the number of patients requiring rescue propofol and flurbiprofen were recorded. Additionally, the time spent under the target level of sedation, postoperative hemodynamics, and the total does of propofol during the postoperative 24 h were recorded. RESULTS: The data showed the SLNB group had a significantly lower incidence of moderate to severe cough and agitation (p < 0.05), and a longer sedation time (p < 0.05). The number of patients required rescue propofol and flurbiprofen, as well as the hemodynamic changes, were significantly different between the two groups (p < 0.05). CONCLUSION: The use of UG-SLNB is associated with reduced incidence of postoperative cough. Moreover, SLNB can enhance the efficacy of postoperative sedation with need of fewer agents postoperatively. CLINICAL TRIAL REGISTRATION: ChiCTR2000039982.

Effect of erector spinae plane block with different doses of dexmedetomidine as adjuvant for ropivacaine on the postoperative quality of recovery after video-assisted thoracoscopic lobectomy surgery: a randomized controlled trial.

BACKGROUND: Erector spinae plane block (ESPB) improves postoperative analgesia and significantly enhances the quality of recovery (QoR) after video-assisted thoracoscopic lobectomy surgery (VATLS). However, it is not known whether the use of dexmedetomidine (Dex) as an adjunct for ropivacaine to ESPB affects the QoR after VATLS. The purpose of this study was to explore the effects of different Dex dosages as an adjunct for ropivacaine in combination with ultrasound-guided ESPB on the quality of postoperative recovery in patients with VATLS. METHODS: In this single-center, double-blind, randomized study, 120 patients between the ages of 18 and 65 who were scheduled for VATLS from december 2021 and october 2022 in our hospital under general anesthesia were randomly divided into three groups: ultrasound-guided ESPB with 30 mL of 0.5% ropivacaine (Group R), ultrasound-guided ESPB 0.5% ropivacaine plus 0.5 µg/kg Dex (Group RD1), and ultrasound-guided ESPB 0.5% ropivacaine plus 1.0 µg/kg Dex (Group RD2), ultrasound-guided ESPB was administrated at the T5 vertebral level before surgery. The primary outcome was the QoR-15 score 24 h after the surgery. The secondary outcomes included the QoR-15 scores at 12 h, 48 h, and 72 h after the operation, visual analogue scale (VAS) scores at 8 h, 12 h, 24 h, and 48 h after surgery, cumulative flurbiprofen consumption, postoperative nausea and vomiting (PONV), postoperative bradycardia, and hypotension. RESULTS: The QoR-15 scores were higher in group RD2 than the R and RD1 groups on postoperative day 1 (P < 0.05), in addition, no significant difference was found in the QoR-15 scores between groups R and RD1 on postoperative day 1. The VAS scores were significantly lower in group RD2 than in groups RD1 and group R 12-24 h after surgery (P < 0.05). No significant differences were observed in the QoR-15 and VAS scores at 48 and 72 h after surgery between the three groups. The cumulative flurbiprofen consumption was markedly reduced during the 72 h after surgery in the RD2 group (P < 0.05). The incidence of postoperative nausea and vomiting was lower in the RD2 group (P < 0.05). CONCLUSIONS: The combination of 1 µg/kg dexmedetomidine as an adjunct with 0.5% ropivacaine 30 ml for erector spinae plane block significantly improved the postoperative quality of recovery and provided better postoperative analgesia on postoperative day 1 in patients undergoing Video-assisted thoracoscopic lobectomy surgery. However, dexmedetomidine (1 µg/kg) as an adjunct for ropivacaine combined with erector spinae plane block did not enhance the postoperative quality of recovery at 48 and 72 h postoperatively. TRIAL REGISTRY NUMBER: The number of this clinical trial registry is ChiCTR2100053230, date of registration: 16/11/ 2021).

Triphenyltin(IV) Carboxylates with Exceptionally High Cytotoxicity against Different Breast Cancer Cell Lines.

Organotin(IV) carboxylates are a class of compounds explored as alternatives to platinum-containing chemotherapeutics due to propitious in vitro and in vivo results, and distinct mechanisms of action. In this study, triphenyltin(IV) derivatives of non-steroidal anti-inflammatory drugs (indomethacin (HIND) and flurbiprofen (HFBP)) are synthesized and characterized, namely [Ph3Sn(IND)] and [Ph3Sn(FBP)]. The crystal structure of [Ph3Sn(IND)] reveals penta-coordination of the central tin atom with almost perfect trigonal bipyramidal geometry with phenyl groups in the equatorial positions and two axially located oxygen atoms belonging to two distinct carboxylato (IND) ligands leading to formation of a coordination polymer with bridging carboxylato ligands. Employing MTT and CV probes, the antiproliferative effects of both organotin(IV) complexes, indomethacin, and flurbiprofen were evaluated on different breast carcinoma cells (BT-474, MDA-MB-468, MCF-7 and HCC1937). [Ph3Sn(IND)] and [Ph3Sn(FBP)], unlike the inactive ligand precursors, were found extremely active towards all examined cell lines, demonstrating IC50 concentrations in the range of 0.076-0.200 µM. Flow cytometry was employed to examine the mode of action showing that neither apoptotic nor autophagic mechanisms were triggered within the first 48 h of treatment. However, both tin(IV) complexes inhibited cell proliferation potentially related to the dramatic reduction in NO production, resulting from downregulation of nitric oxide synthase (iNOS) enzyme expression.

Anti-inflammatory mechanisms of eucalyptol rich Eucalyptus globulus essential oil alone and in combination with flurbiprofen.

Inflammation is the core contributor in the pathogenesis of various acute and chronic illness including appendicitis, bronchitis, arthritis, cancer and neurological diseases. NSAIDs, commonly used medications for inflammatory diseases, on prolonged use cause GI bleeding, ulcers and many more issues. Plant-based therapeutic agents including essential oils in combination with low-dose synthetic drugs have been shown to produce synergistic effects and reduce complications of synthetic drugs. This study was designed to evaluate the anti-inflammatory, analgesic and anti-pyretic properties of Eucalyptus globulus essential oil alone and in combination with flurbiprofen. GC-MS analysis was performed to screen chemical composition of oil. In vitro anti-inflammatory assay (membrane stabilization assay) and in vivo inflammatory acute (carrageenan and histamine-induced paw oedema) and chronic (cotton pellet-induced granuloma and Complete Freund's adjuvant-induced arthritis) models were performed to check anti-inflammatory properties. Acetic acid-induced algesia and yeast-induced pyrexia models were performed to check analgesic and anti-pyretic properties. qRT-PCR was performed to study the effect of treatments on the expression of inflammatory biomarkers. GC-MS analysis of E. globulus essential oil showed the presence of eucalyptol along with other active biomolecules. 500 + 10 mg/kg of oil-drug combination showed significantly (p < 0.05) better in vitro membrane stabilization effects as compared with groups treated with 500 mg/kg of E. globulus oil and 10 mg/kg of Flurbiprofen alone. 500 + 10 mg/kg of oil-drug combination showed significantly (p < 0.05) better anti-inflammatory, analgesic and antipyretic effects as compared to 500 mg/kg of E. globulus oil alone in all in vivo models. When comparison was done between 500 + 10 mg/kg of oil-drug combination-treated and 10 mg/kg Flurbiprofen-treated group, the former group showed significantly (p < 0.05) better anti-inflammatory and anti-pyretic effects, but there were non-significant differences in the analgesic model. Animal group treated with 10 mg/kg of Flurbiprofen showed significantly (p < 0.05) better anti-inflammatory and analgesic effects than group treated with 500 mg/kg of oil alone while, there were non-significant differences in anti-pyretic effects. qRT-PCR analysis showed significant (p < 0.05) down-regulation in the expression of IL-4 and TNF-α in serum samples of animals treated with 500 + 10 mg/kg of oil-drug combination as compared to the diseased control (arthritic) group. Overall, the current research demonstrates that Eucalyptus globulus essential oil in combination with flurbiprofen showed better anti-inflammatory, analgesic and anti-pyretic effects than oil and flurbiprofen alone which is attributed to the down-regulation of pro-inflammatory biomarkers (IL-4 and TNF-α). Further studies are required to formulate a stable dosage form and to check the anti-inflammatory efficacy in different inflammatory disorders.

Phenylalanine conjugated supramolecular hydrogels developed from the mafenide and flurbiprofen multidrug for biological applications.

A well-known nonsteroidal anti-inflammatory drug (NSAID), flurbiprofen (FLR), was first conjugated individually with two naturally occurring amino acids such as L-phenylalanine (PHE) and L-alanine (ALA). These covalent amidic bioconjugates were further reacted individually with mafenide (a drug for treating burn wounds) and amantadine (an antiviral drug) to develop primary ammonium monocarboxylate (PAM) salts. Interestingly, both the PHE-containing multidrug salts exhibited significant gelation ability with various solvents including biologically potent water or methyl salicylate (MS). The isolated hydrogel (HG) as well as all the organogels obtained from multidrug gelators were extensively characterized by dynamic rheology and rheoreversibility studies. The hydrogel of FLR·PHE·MAF and MS gels of FLR·PHE·AMN/FLR·AMN were also selectively characterized by table-top and FEG-TEM analyses. The temperature-dependent 1H-NMR spectroscopy of the selected HG further provided insights into the gelation mechanism and the only isolated single-crystal of the weakly diffracted gelator FLR·AMN also revealed the presence of 1D hydrogen-bonded networks. The pure hydrogelator FLR·PHE·MAF salt (which is also an ambidextrous gelator) was found to be promising in both mechanical (rheoreversible) and biological applications and was found to be effective in cytotoxicity, biocompatibility, anti-cancer activity (MTT and cell migration assay), antibacterial response (zone inhibition, turbidity, INT, and resazurin assay) and haemolysis studies.

The Role of the Transient Atropisomerism and Chirality of Flurbiprofen Unveiled by Laser-Ablation Rotational Spectroscopy.

The combination of atropisomerism and chirality in flurbiprofen is shown to be relevant concerning its pharmacological activity. The two most stable conformers of a total of eight theoretically predicted for each R- or S- flurbiprofen enantiomers have been isolated in the cooling conditions of a supersonic jet and structurally characterized by laser ablation Fourier transform microwave spectroscopy. The detected conformers, whose structure is mainly defined by three dihedral angles, only differ in the sign of the phenyl torsion angle giving rise to Sa and Ra atropisomers. A comparison with the structures available for the R- and S- enantiomers complexed to COX isoforms reveals that the enzymes select only the Sa atropisomers, resulting in a diastereoisomer-specific recognition. The most stable gas phase conformer is exclusively selected when using the S- enantiomer while the second is recognized only for the R- enantiomer. These experimental results highlight the importance of atropisomerism in drug design.

Comparison of hyaluronic acid, hypochlorous acid, and flurbiprofen on postoperative morbidity in palatal donor area: a randomized controlled clinical trial.

OBJECTIVE: This study aims to evaluate the effects of topical hyaluronic acid (HA), hypochlorous acid (HOCl), and flurbiprofen on postoperative morbidity of palatal donor sites after free gingival graft (FGG) surgery. MATERIALS AND METHODS: Sixty patients requiring FGG were randomly assigned into four groups: control, HA gel (600 mg/100 g high molecular weight hyaluronic acid), HOCl spray (170-200 ppm, ph7.1), flurbiprofen spray (0.075gr flurbiprofen). Topical agents were applied for 14 days, according to groups. Patients were followed for 28 days. Palatal healing was assessed with the Laundry wound healing index (WHI). Complete epithelization (CE) was evaluated with photographs and H2O2 bubbling. Pain, burning sensation, chewing efficacy, and tissue color match (CM) were evaluated using a visual analog scale (VAS). Postoperative analgesic consumption and delayed bleeding (DB) were also recorded. RESULTS: HA provided better WHI values on the 7th, 14th, and 21st days compared to the other groups, respectively (p < 0.05). CE was formed on the 21st day in the HA group but on the 28th day in the other groups. HOCl and flurbiprofen groups were not different from the control group or each other in terms of WHI. HOCl had the lowest VAS scores of all time periods. DB was not observed in any group. Significantly fewer analgesics were taken in the topical agent-applied groups compared to the control group. CONCLUSIONS: HA exhibits a positive impact on the epithelization of palatal wound healing and color matching. HOCl and flurbiprofen provided less pain; however, they might have negative effects on palatal wound healing. CLINICAL RELEVANCE: As a result of obtaining free gingival grafts from palatal tissue for mucogingival surgical procedures, secondary wound healing of the donor area occurs. This wound in the palatal region can cause discomfort and pain every time patients use their mouths. The use of HA can reduce postoperative complications by accelerating wound healing and reducing pain. The topical use of flurbiprofen and HOCl can reduce patients' pain.

Development of a series of flurbiprofen and zaltoprofen platinum(IV) complexes with anti-metastasis competence targeting COX-2, PD-L1 and DNA.

To develop new anti-metastasis chemotherapeutic drugs, a series of flurbiprofen (FLP) and zaltoprofen (ZTP) platinum(IV) complexes targeting COX-2, PD-L1 and DNA was prepared and investigated. Complex 2 with dual FLP ligands displays promising antitumor activities in vitro and exhibits much potential in overcoming drug resistance. More importantly, the antitumor evaluation in vivo demonstrates that complex 2 possesses promising inhibition of cancer growth and metastasis simultaneously. Further investigation of the mechanism revealed the multi-specific antitumor function of complex 2. It exerts remarkable DNA damage after reduction to platinum(II) complex, and up-regulates the expression of p53 and γ-H2AX. Then, complex 2 promotes mitochondria-mediated apoptosis effectively by activating the Bcl-2/Bax/caspase3 pathway. Furthermore, inflammation in tumor tissues is restrained by the suppression of enzymes COX-2, MMP-9, NLRP3 and caspase1, which would favor the inhibition of tumor metastasis. Moreover, compound 2 boosts T-cell immunity by restraining PD-L1 expression, and further improving the density of CD3+ and CD8+ T cells in tumor tissues.

Effects of Knee Debridement with Flurbiprofen on Knee Function, Inflammatory Levels, and Bone Metabolism Activity in Patients with Knee Osteoarthritis.

Objective: The objective of this study is to explore the effects of knee debridement with flurbiprofen on the knee function, inflammatory levels, and bone metabolism activity in patients with knee osteoarthritis. Methods: 110 patients with knee osteoarthritis who underwent arthroscopic debridement in our hospital from 2020.01 to 2022.01 were selected for retrospective analysis. Based on whether or not flurbiprofen was used in combination during the perioperative phase, the patients were divided into the control group (only arthroscopic debridement of the knee) and the research group (flurbiprofen with arthroscopic debridement of the knee), with 55 cases in each group. The indexes such as knee function, inflammatory levels, and bone metabolism activity of the two groups were analyzed. Results: According to hospital for special surgery (HSS) evaluation for knee function, most patients in the control group were assessed as "moderate," while patients in the research group were mainly focused on "excellent" and "good," and their excellent and good rates were remarkably higher than those in the control group (P < 0.05). There were no significant variations in bone metabolism indices such as osteoprotegerin levels (OPG), insulin-like growth factor-1 (IGF-1), ß-isomerized C-terminal telopeptide (ß-CTX), and receptor activator of nuclear factor-κB ligand (RANKL) before treatment between both groups (P > 0.05), with higher OPG, IGF-1 levels, and remarkably lower ß-CTX, RANKL levels in the research group than those in the control group after treatment (P < 0.05). There were no remarkable differences in pain between both groups before treatment (P > 0.05), while at 24 h and 48 h after surgery, the VAS scores in the research group were remarkably lower than those in the control group (P < 0.05). In terms of inflammatory factors, the levels of interleukin-1ß (IL-1ß), tumor necrosis factor-α (TNF-α), and cyclooxygenase-2 (COX-2) in the research group were remarkably lower than those in the control group after treatment (P < 0.05). Conclusion: Arthroscopy coupled with flurbiprofen provides a good analgesic effect in the therapeutic treatment of patients with knee osteoarthritis, which contributes to the recovery of knee function with definite results. Its mechanism may be associated with the control of inflammatory response and the regulation of bone metabolism disorder.

Effects of multimodal analgesia of flurbiprofen axetil, nalbuphine and patient controlled intravenous analgesia on inflammatory factor levels and stress response in patients after laparoscopic radical gynecological malignancy surgery.

To evaluate the efficacy of multimodal analgesia of flurbiprofen axetil, nalbuphine hydrochloride and patient controlled intravenous analgesia (PCIA) on inflammatory factor levels and stress response in patients after laparoscopic radical gynecological malignancy surgery. The data of 100 patients admitted to our hospital from May 2019 to May 2020 for laparoscopic radical gynecological malignancy surgery were retrospectively analyzed and they were assigned (1:1) to either an experimental group or a control group according to the alphabetical order of their initials. The experimental group was given preemptive analgesia with flurbiprofen axetil, postoperative analgesia with nalbuphine hydrochloride, and PCIA and the control group was given conventional analgesic measures. The pain scores at 1h, 6h, 12h, 24h and 48h postoperatively in the experimental group were remarkably lower than those in the control group (P<0.001). The experimental group showed significantly lower inflammatory factor levels, pain mediator levels and stress response indexes in the morning before surgery, 1d, and 2d after surgery than the control group (P<0.001). The multimodal analgesia of flurbiprofen axetil, nalbuphine hydrochloride and PCIA can effectively alleviate the stress response and inflammatory response in patients after radical gynecologic malignancy surgery and the patients' pain perception is reduced with a high safety profile.

N-acetylcysteine functionalized chitosan oligosaccharide-palmitic acid conjugate enhances ophthalmic delivery of flurbiprofen and its mechanisms.

An N-acetylcysteine functionalized chitosan oligosaccharide-palmitic acid conjugate (NAC-COS-PA) with bioadhesive and permeation promoting properties was synthesized to enhance transocular drug delivery. Flurbiprofen (FB) loaded self-assembled NAC-COS-PA nanomicelles (NAC-COS-PA-FB) were prepared and the drug loading was 7.35 ± 0.32%. Human immortalized corneal epithelial (HCE-T) cell cytotoxicity and hen's egg test-chorioallantoic membrane assays confirmed that the conjugate had good biocompatibility. The transportation efficiency of coumarin-6 (C6) loaded nanomicelles in the HCE-T cell monolayer was approximately 1.97 times higher than that of free C6. Decreased intracellular Ca2+ concentration and cell membrane potential, increased cell membrane fluidity, and reversible changes in the F-actin cytoskeleton are presumed to be responsible for the enhanced drug permeation. NAC-COS-PA exhibited strong binding capacity with mucin and rabbit eyeball. In vivo pharmacokinetics indicated that the area under the curve (AUC0-6 h) and the maximum concentration (Cmax) of NAC-COS-PA-FB were approximately 1.92 and 2.44 times that of the FB solution, respectively. NAC-COS-PA-FB demonstrated the best in vivo anti-inflammatory efficacy compared to unfunctionalized nanomicelles (COS-PA-FB) and FB solution. Consequently, NAC-COS-PA appears to be a promising bioadhesive carrier for ophthalmic delivery.

Analgesic effects of sufentanil in combination with flurbiprofen axetil and dexmedetomidine after open gastrointestinal tumor surgery: a retrospective study.

BACKGROUND: To investigated the effects of sufentanil in combination with flurbiprofen axetil and dexmedetomidine for patient-controlled intravenous analgesia (PCIA) on patients after open gastrointestinal tumor surgery, and compared this combination with traditional PCIA with pure opioids or epidural analgesia (PCEA). METHODS: Patients (n = 640) who underwent open gastrointestinal tumor surgery and received patient-controlled analgesia (PCA) were included. According to the type of PCA, patients were assigned to three groups: MPCIA (PCIA with sufentanil, flurbiprofen axetil, dexmedetomidine and metoclopramide), OPCIA (PCIA with sufentanil, tramadol and metoclopramide) and PCEA group (PCEA with sufentanil and ropivacaine). The characteristics of patients, intraoperative use of analgesics, postoperative visual analogue scale (VAS), postoperative adverse reactions and postoperative recovery were collected. The primary outcome was postoperative VAS score. One-way ANOVA, Kruskal-Wallis H test, Fisher exact probability method, and binary logistic regression analysis were used for analysis. RESULTS: There were no significant differences in the characteristics of patients, operation time, tumor site and the use of postoperative rescue analgesics among the groups. In the first two days after open gastrointestinal tumor surgery, the VAS (expressed by median and interquartile range) of MPCIA (24th h, resting: 1,1; movement: 3,2. 48th h, resting: 0,1; movement: 2,1.) and PCEA (24th h, resting: 0,1; movement: 2,1. 48th h, resting: 0,1; movement: 2,2.) groups were significantly lower than those of OPCIA group (24th h, resting: 2.5,2; movement: 4,2. 48th h, resting: 1.5,1.75; movement: 3,1.) (all p <  0.01). The incidence of postoperative nausea and vomiting in MPCIA group was 13.6% on the first day after surgery, which was significantly higher than that in PCEA group. There was no significant difference in the incidence of other postoperative adverse events. Higher intraoperative sufentanil dosage (OR (95%CI) = 1.017 (1.002-1.031), p = 0.021), lower body mass index (OR (95%CI) = 2.081 (1.059-4.089), p = 0.033), and tumor location above duodenum (OR (95%CI) = 2.280 (1.445-3.596), p <  0.001) were associated with poor postoperative analgesia. CONCLUSIONS: The analgesic effects of PCIA with sufentanil in combination with flurbiprofen axetil and dexmedetomidine on postoperative analgesia was better than that of traditional pure opioids PCIA, and similar with that of PCEA.

Developmental Cardiotoxicity and Hepatotoxicity of Flurbiprofen Axetil to Zebrafish Embryo.

Flurbiprofen axetil (FA) is a nonsteroidal targeted analgesic and widely used for postoperative analgesia and cancer analgesia. Extensive works have been done in the evaluation of FA's clinical analgesic effect on adults. Along with the increase of FA usage, the potential toxicity and molecular mechanism in embryo development need to be better understood. In this article, multiple embryonic development indexes of zebrafish were introduced to evaluate the FA toxicity to provide clinical guidance for gravidas medicine. We performed a zebrafish embryo toxicity (ZFET) test by exposing embryos to a series of concentration gradients of FA medium starting from 24 hours postfertilization (hpf). The mortality rate, hatching rate, and malformation rate of drug-treated zebrafish were assessed at 72, 96, and 120 hpf. Effects of ≤10% lethal concentration (LC10) of FA on embryogenesis were evaluated by eye area, body length, and yolk sac area. A 0.5 µg/mL or fewer FA treatment did not show any adverse effects, but the LC10 FA significantly caused zebrafish malformation. Organ disorders, including slow heart rate, enlarged pericardium, and liver atrophy, were found in the dysplasia individuals when compared with control. TUNEL assay suggested that apoptotic cells in malformation embryos were produced by FA and the increasing dosage exacerbated apoptosis. Quantitative real-time polymerase chain reaction revealed that expressions of cardiac development-associated transcription factors, liver development-related genes, and apoptosis regulating genes were aberrant. These results indicate that the ZFET can be applied in the FA toxicity test, and a low lethal dose of FA is harmful to zebrafish embryogenesis, especially in embryo carcinogenesis and hepatogenesis.