Xefo (lornoxicam) / Old API Wind-down, Takeda - LARVOL DELTA

Multimodal evaluation of lipoxygenase-targeting NSAIDs using integrated in vitro, SAR, in silico, cytotoxicity towards MCF-7 cell line, DNA docking and MD simulation approaches. (PubMed, Int J Biol Macromol) - "We reported earlier that several NSAIDs, including naproxen, aspirin and acetaminophen, inhibited lipoxygenase (LOX) enzyme at sub-micromolar concentrations...Aceclofenac (IC50 0.85 ± 0.06 μM) was the most active drug, followed by indomethacin (IC50 1.13 ± 0.07 μM), meloxicam (IC50 1.94 ± 0.07 μM) and ketorolac (IC50 9.26 ± 0.82 μM). Celecoxib (IC50 15.81 ± 0.71 μM), lornoxicam (IC50 16.54 ± 0.28 μM) and nimesulide (IC50 19.87 ± 0.85 μM) showed excellent inhibitory profiles. Flurbiprofen (IC50 21.73 ± 0.93 μM) and etoricoxib (IC50 24.93 ± 0.64 μM) moderately inhibited the target enzyme...Density functional theory (DFT) and ESP studies, MD simulations and MMPBSA free energy calculations further reiterated the stability of ligand-receptor complexes. Overall, these findings highlight the potential of targeted NSAIDs as dual COX/LOX inhibitors with broader therapeutic relevance in inflammatory disorders."

Journal • Preclinical • Breast Cancer • Oncology • Solid Tumor

In vitro-in vivo scaling of cytochrome P450-mediated metabolic clearance using a relative activity factor approach. (PubMed, Drug Metab Dispos) - "We selected multiple probe substrates for CYP1A2 (caffeine, tizanidine, phenacetin), CYP2C9 ((S)-acenocoumarol, glimepiride, lornoxicam, tolbutamide, (S)-warfarin), CYP2C19 ((S)-lansoprazole, omeprazole, pantoprazole), CYP2D6 (desipramine, metoprolol, nebivolol, tolterodine), and CYP3A4 (alprazolam, felodipine, midazolam, nisoldipine, sildenafil, triazolam) to calculate the representative RAF value for each P450 isoform based on the in vivo-to-in vitro clearance ratio of the multiple probe substrates...The fm values of the responsible P450 isoform(s) could be well predicted for mexiletine, tamsulosin, risperidone, celecoxib, and glibenclamide...By applying relative activity factor values obtained from multiple probe substrates, this study was able to quantitatively predict the in vivo clearances mediated by CYP1A2, CYP2C9, CYP2C19, CYP2D6, and CYP3A4. This simple, practical method will help optimize metabolic clearances via the major cytochrome P450..."

Journal • Preclinical • CYP1A2 • CYP2C19 • CYP2C9 • CYP3A4

Nonsteroidal anti-inflammatory drugs (NSAIDs) for acute renal colic. (PubMed, Cochrane Database Syst Rev) - "NSAIDs may reduce pain in adult patients with renal colic compared to placebo. Comparing one NSAID against another, IV ketorolac may be less effective than IV ibuprofen, and pirprofen may result in less need for rescue medication than indomethacin. The intravenous route of administration is probably similar to the intramuscular route but may be better than the rectal route. The evidence is uncertain regarding the potential harms of NSAIDs. We were not able to perform subgroup analysis based on our predefined criteria because there were no eligible studies."

Clinical • Journal • Review • Inflammation • Pain • Renal Calculi • Urolithiasis

Revolutionizing Drug Delivery: A Design Professional's Approach to Drug-loaded Transferosomal Vesicles for Transdermal Use. (PubMed, Pharm Nanotechnol) - "The study concludes that formulation TDP-8, which incorporates 3g of Aloe vera leaf mucilage (AVLM) and lime oil (LO) as permeability enhancers, demonstrated favorable discharge characteristics. This indicates its potential as an effective transdermal delivery system for LXM and TCS, offering a promising substitute for pain and inflammation relief while minimizing gastric irritation. The study succeeded in developing and evaluating transferosomal transdermal patches for LXM and TCS, providing an alternative delivery method that minimizes gastric irritation."

Journal • Inflammation • Pain

Formulation, Optimization, and Evaluation of Lornoxicam-Loaded Novasomes for Targeted Ulcerative Colitis Therapy: In Vitro and In Vivo Investigations. (PubMed, J Drug Target) - "At the same time, it elevated Silent information regulator-1(SIRT-1) and reduced glutathione (GSH) colon contents. Thus, the current study suggested that the formulation of LOR- Novas may be a viable treatment for ulcerative colitis."

Journal • Preclinical • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis • TLR4

Open observational study with a retrospective analysis of the efficacy and tolerability of aceclofenac in patients with acute non-specific low back pain (PubMed, Zh Nevrol Psikhiatr Im S S Korsakova) - "The use of NSAIDs for low back pain is effective and safe. Aceclofenac and nimesulide are superior to dexketoprofen and lornoxicam in terms of functional activity associated with low back pain and health-related quality of life. Aceclofenac demonstrated the most favorable safety profile and a lower risk of chronicity (compared to nimesulide and lornoxicam) and recurrence (compared to dexketoprofen) of low back pain."

Journal • Observational data • Retrospective data • Back Pain • Cardiovascular • Gastrointestinal Disorder • Lumbar Back Pain • Musculoskeletal Diseases • Musculoskeletal Pain • Pain

Development of Immediate Release Tablet Formulations of Lornoxicam with Hot Melt Extrusion Based Three-Dimensional Printing Technology. (PubMed, Drug Dev Ind Pharm) - "Despite the availability of conventional immediate release LRX tablets, this newly developed formulation offers the potential to be modulated for personalized theraphy via the 3D printing technique. This study demonstrates the feasibility of HME-based FDM printing technology for producing immediate-release LRX tablets with consistent quality, highlighting the utilization of MCC II as a disintegrating agent that enhances LRX dissolution in this process."

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Enhancing Postoperative Analgesia After Cesarean Section: Insights Into Transversus Abdominis Plane Block, Intrathecal Opioids, and Other Analgesic Techniques. (PubMed, Cureus) - "Bilateral TAP block has the potential to effectively enhance postoperative analgesia and reduce the need for systemic opioids after both GA and SA. Compared to ITF, ITM provides a higher quality and longer duration of analgesia with minimal analgesic-related side effects. Further studies to find an optimal analgesic protocol with few to no side effects are warranted."

Journal • Anesthesia • Pain

A prospective split-mouth clinical study: comparison of the effect of lornoxicam and etodolac on postoperative sequels following lower third molar surgery. (PubMed, Oral Maxillofac Surg) - "Based on the results obtained in the present study, ıt has been verified that both lornoxicam and etodolac were adequately effective in the management of pain following third molar surgery. Lornoxicam and etodolac had similar impacts on pain, edema and trismus after impacted lower third molar surgical extractions."

Journal • Surgery • Pain

A potential cocrystal strategy to tailor in-vitro dissolution and improve Caco-2 permeability and oral bioavailability of berberine. (PubMed, Int J Pharm) - "To address these challenges, we developed a BER and lornoxicam cocrystal (BLCC) by a solvent evaporation method and characterized it using X-ray diffraction, differential scanning calorimetry and thermogravimetric analysis...BLCC has the potential to tailor the dissolution behavior, improve intestinal permeability, and boost the bioavailability of BER. This indicates that the cocrystal strategy holds promise as an effective approach to improving the oral absorption and bioavailability of active pharmaceutical molecules with low permeability during drug development."

Journal • Preclinical • Diabetes • Metabolic Disorders • Oncology • Pain

Aloe vera leaf mucilage and lemon oil as potential penetration-enhancing agents to increase lornoxicam transdermal administration using nano vesicular gel. (PubMed, Pak J Pharm Sci) - "In light of its ability to administer LXM across the skin sustainably while producing a tolerable analgesic effect. The study concludes that the artificial transdermal LXM delivery system is a suitable substitution for the oral route."

Journal • Pain

Drug induced Fuchs Syndrome - A novel case report (EADV 2024) - "After 5 days, he reported to otolaryngology clinic, with history of fever and severe painful oral ulcerations associated with odynophagia and was managed with parenteral lornoxicam and ceftriaxone...He was treated with injection dexamethasone (8mg) stat, oral prednisolone 30mg/day, fluconazole 150mg and miconazole oral gel (to prevent/treat oral candidiasis); fusidic acid ointment and chlorhexidine mouthwash... The author believes that FS being a variant of EM major or SJS, can also be induced by those drugs which are known to cause EM major or SJS especially NSAIDs as in the present case. This condition is under- diagnosed as well as under-reported probably due to multiple terminologies involved and thus causing diagnostic confusion. Considering it to be EM major can avoid such controversy."

Case report • Clinical • Candidiasis • Dermatology • Herpes Simplex • Infectious Disease • Mucositis • Otorhinolaryngology • Pain • Pneumonia • Respiratory Diseases • Steven-Johnson Syndrome • CRP

Tolerance to NSAIDs in Brain Limbic Areas (IASP 2024) - "Under anesthesia with intramuscular administration of ketamine, stainless steel guide cannula was stereotaxically implanted bilaterally into the brain limbic areas for injection NSAIDs (diclofenac, ketorolac, ketoprofen, and lornoxicam) and pre- or post-administration of a combined opioid receptor antagonist (naloxone, or CTOP) and cannabinoid receptor (CB1) antagonist (AM-251). Here we confirmed the concept that antinociception and the development of tolerance to NSAIDs are mediated via endogenous opioid and cannabinoid systems involving the descending pain modulatory circuits attenuating pain behavior in rats – defensive paw withdrawal reflexes at the spinal cord level."

Anesthesia • Pain

Formulation and Characterization of Emulgel Lornoxicam Containing Lemon Grass Oil as Penetration Enhancer. (PubMed, Antiinflamm Antiallergy Agents Med Chem) - "The emulgel of the poorly water-soluble drug (lornoxicam) was formulated. The components and their optimum ratio for the formulation of microemulsion were obtained by solubility studies and droplet size analysis. Thus, microemulsion can be regarded as a more feasible dose delivery system for lornoxicam than the currently marketed tablet, capsule, and injection formulations. Optimized microemulsion of lornoxicam was incorporated into the gel base. Therefore, it may be concluded that emulgel of lornoxicam can be used as a controlled-release dosage form of the drug for local application in rheumatoid arthritis."

Journal • Immunology • Inflammatory Arthritis • Rheumatoid Arthritis • Rheumatology

Optimizing lornoxicam-loaded poly(lactic-co-glycolic acid) and (polyethylene glycol) nanoparticles for transdermal delivery: ex vivo/in vivo inflammation evaluation. (PubMed, Nanomedicine (Lond)) - "LOX exhibited a permeation rate of 70-94% from the nanoparticle-infused gel, demonstrating favorable biocompatibility at the cellular level. The formulated gel, enriched with nanoparticles, holds promising prospects for drug-delivery systems and promising improved therapeutic outcomes for LOX."

Journal • Preclinical • Gastrointestinal Disorder • Immunology • Inflammation • Osteoarthritis • Pain • Rheumatoid Arthritis • Rheumatology

Dispersion characteristics of arc-axis waveguides. (PubMed, Ultrasonics) - "Therefore, in this paper, a novel semi-analytical finite element method in cylindrical coordinates (SAFEM-CC) is established and we focus on the dispersion characteristics of arc-axis waveguides...Finally, the correctness of the proposed method and the dispersion characteristics of arc-axis waveguides are verified by a large number of experiments. The main conclusions are as follows: the waveform transmission laws of the guided wave in arc-axis waveguides at each frequency agree with the dispersion curve; the theoretical wavestructure gives the distribution law of the amplitude within the cross-section; when the axis is arc, the displacement of the wavestructure on the inner and outer sides does not have symmetry, and the difference between the left and right sides gradually increases as the radius decreases."

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Identifying alkaline phosphatase inhibitory potential of cyclooxygenase-2 inhibitors: Insights from molecular docking, MD simulations, molecular expression analysis in MCF-7 breast cancer cell line and in vitro investigations. (PubMed, Int J Biol Macromol) - "Three COX-2 inhibitors including nimesulide, piroxicam and lornoxicam were evaluated for the inhibition of APs using in silico and in vitro methods...Molecular expression analysis of TNAP enzyme in the breast cancer cell line MCF-7 exhibited 0.24-fold downregulation with 5 μM nimesulide as compared with 0.26-fold standard 10 μM levamisole. In vitro assays against human placental AP (hPAP) displayed potent inhibitions of these drugs with IC50 values of 0.52 ± 0.02 μM to 3.46 ± 0.13 μM and similar results were obtained for bovine intestinal AP (bIAP). The data when generalized collectively emphasizes that the inhibition of APs by COX-2 inhibitors provides another target to work on the development of anticancer drugs."

Journal • Preclinical • Alzheimer's Disease • Breast Cancer • CNS Disorders • Hepatology • Oncology • Solid Tumor

Desosomes and desimicelles - a novel vesicular and micellar system for enhanced oral delivery of poorly soluble drug: Optimization of in vitro characteristics and in vivo performance. (PubMed, Eur J Pharm Biopharm) - "Lornoxicam (LRX) is a BCS class II anti-inflammatory with limited aqueous solubility and rapid clearance...LRX-DES-M also showed a better reduction in COX2, PGE2, and TNF-α (1.25-fold, 1.24-fold, and 1.36-fold inhibition), respectively, compared to LRX-DES-V. We can conclude that LRX-DES-V and LRX-DES-M showed better effects than all other groups and that LRX-DES-M might be more effective than LRX-DES-V."

Journal • Preclinical • Inflammation • TNFA

Efficacy of Lornoxicam as a Pre-emptive Analgesic in Mandibular Third Molar Surgery - A Comparative Study. (PubMed, Ann Maxillofac Surg) - "When compared to Group A, Group B had a lower need for rescue analgesics within the first 24 h postoperatively. Following mandibular third molar surgery, pre-emptive use of lornoxicam is effective in reducing post-operative pain and reducing the need for rescue analgesic consumption."

Journal • Surgery • Pain

Simultaneous determination of 14 analgesics in postoperative analgesic solution by HPLC-DAD and LC-MS/MS. (PubMed, BMC Chem) - "A green, efficient, sensitive and accurate detection method by HPLC-DAD and LC-MS/MS was developed and validated for the quantification of morphine, hydromorphone, oxycodone, ketamine tramadol, dezocine, ropivacaine, remifentanil, butorphanol, bupivacaine, droperidol, fentanyl, lornoxicam and sufentanil. The proposed method has been successfully applied in the clinic and provides a strong technical basis for the quantitative detection of these 14 mixtures for detecting drug abuse, and for studying the stability and compatibility of analgesic solutions. The proposed methods were validated against ICH guidelines."

Journal • Pain

Magnetic targeting of lornoxicam/SPION bilosomes loaded in a thermosensitive in situ hydrogel system for the management of osteoarthritis: Optimization, in vitro, ex vivo, and in vivo studies in rat model via modulation of RANKL/OPG. (PubMed, Drug Deliv Transl Res) - "In addition, the histopathological evaluation of knee joint tissues showed a remarkable improvement in the injured joint tissues. The results proved that the developed LSB could be a promising IM drug delivery system for osteoarthritis management."

Journal • Preclinical • Immunology • Osteoarthritis • Pain • Rheumatology • TNFRSF11A • TNFRSF11B

Drug repurposing analysis for colorectal cancer through network medicine framework: Novel candidate drugs and small molecules. (PubMed, Cancer Invest) - "Based on the gene module, polyethylene glycol, gallic acid, pyrazole, cordycepin, phenothiazine, pantoprazole, cysteamine, indisulam, valinomycin, trametinib, BRD-K81473043, AZD8055, dovitinib, BRD-A17065207, and tyrphostin AG1478 presented as drugs and small molecule candidates previously studied in the CRC. Lornoxicam, suxamethonium, oprelvekin, sirukumab, levetiracetam, sulpiride, NVP-TAE684, AS605240, 480743.cdx, HDAC6 inhibitor ISOX, BRD-K03829970, and L-6307 are proposed as novel drugs and small molecule candidates for CRC."

Journal • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • TERC

Formulation Development of Lornoxicam Loaded Heat Triggered Ocular In-situ Gel Using Factorial Design. (PubMed, Drug Dev Ind Pharm) - "In Draize's in vivo test, no negative conditions occurred in rats. Therefore, the NL6-CD formulation has the potential to be a favorable option for treating ocular inflammation."

Journal • Inflammation • Ocular Inflammation

Value of indomethacin suppository for preoperative analgesia and anti-inflammation in laparoscopic appendectomy: a protocol of prospective, double-blinded, single-centre, randomised controlled trial in China. (PubMed, BMJ Open) - "The trial was divided into two groups (n=64) using a randomised number table: group A will be given 100 mg of indomethacin suppository rectally and group B will be given 8 mg of intravenous lornoxicam. We will disseminate our study findings at national and international paediatric research conferences. Chinese Clinical Trial Registry (ChiCTR2200062004)."

Journal • Anesthesia • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammation • Inflammatory Bowel Disease • Pain • Pediatrics

Principles of White Analytical Chemistry and Design of Experiments to Stability-Indicating Chromatographic Method for Simultaneous Estimation of Thiocolchicoside and Lornoxicam. (PubMed, J AOAC Int) - "Development of stability-indicating HPTLC method using a novel white analytical chemistry approach and organic solvents with low toxicity potential. Application of the developed method for analysis of the forced degraded sample and fixed-dose combinations of THC and LNX."

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